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Okuda R, Matsushima H, Aoshiba K, Oba T, Kawabe R, Honda K, Amano M. Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis. SPRINGERPLUS 2015; 4:657. [PMID: 26543791 PMCID: PMC4628606 DOI: 10.1186/s40064-015-1455-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 10/20/2015] [Indexed: 12/01/2022]
Abstract
The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other interstitial pneumonia markers were measured. In this study, 30 patients with stable IPF and 11 patients with acute exacerbation of IPF were collected. Mean sICAM-1 levels were 434 ± 139 ng/mL for the stable phase of IPF, 645 ± 247 ng/mL for early phase of acute exacerbation of IPF, 534 ± 223 ng/mL for connective tissue disease-associated interstitial pneumonia, 221 ± 42 for chronic obstructive pulmonary disease, and 150 ± 32 ng/mL in healthy volunteers. For the stable phase of IPF, sICAM-1 levels correlated with Krebs von den Lungen-6 (KL-6) (r value: 0.41; p value: 0.036). Mean sICAM-1 levels were significantly higher in patients with early phase of acute exacerbation of IPF than with stable phase of IPF (p = 0.0199). Multiple logistic analyses indicated that the predictors for early phase of acute exacerbation of IPF were only sICAM-1 and C-reactive protein (odds ratio: 1.0093; 1.6069). In patients with stable IPF, sICAM-1 levels correlated with KL-6; sICAM-1 might be a predictive indicator for prognosis. In the early phase of acute exacerbation of IPF, sICAM-1 might be more useful for diagnosis than other interstitial pneumonia markers.
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Affiliation(s)
- Ryo Okuda
- Department of Respiratory Medicine, Saitama Red Cross Hospital, 8-3-33 Kami-ochiai, Chuo-ku, Saitama, 338-8553 Japan ; Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki Japan
| | - Hidekazu Matsushima
- Department of Respiratory Medicine, Saitama Red Cross Hospital, 8-3-33 Kami-ochiai, Chuo-ku, Saitama, 338-8553 Japan
| | - Kazutetsu Aoshiba
- Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki Japan
| | - Tomohiro Oba
- Department of Respiratory Medicine, Saitama Red Cross Hospital, 8-3-33 Kami-ochiai, Chuo-ku, Saitama, 338-8553 Japan
| | - Rie Kawabe
- Department of Respiratory Medicine, Saitama Red Cross Hospital, 8-3-33 Kami-ochiai, Chuo-ku, Saitama, 338-8553 Japan
| | - Koujiro Honda
- Department of Respiratory Medicine, Saitama Red Cross Hospital, 8-3-33 Kami-ochiai, Chuo-ku, Saitama, 338-8553 Japan
| | - Masako Amano
- Department of Respiratory Medicine, Saitama Red Cross Hospital, 8-3-33 Kami-ochiai, Chuo-ku, Saitama, 338-8553 Japan
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Toiyama Y, Yasuda H, Saigusa S, Tanaka K, Inoue Y, Goel A, Kusunoki M. Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis 2013; 34:2548-57. [PMID: 24001454 DOI: 10.1093/carcin/bgt282] [Citation(s) in RCA: 111] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Slug and Vimentin genes play a critical role in regulating epithelial-mesenchymal transition (EMT) via downregulation of epithelial markers and upregulation of mesenchymal markers. The present study evaluated the clinical significance of Slug and Vimentin expression as potential disease biomarkers in colorectal cancer (CRC). At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. Next, we analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients (Cohort 1) by quantitative real-time reverse transcription-PCR and 208 patients (Cohort 2) by immunohistochemistry. Knockdown of Slug using small interfering RNA in CRC cell lines resulted in inhibition of EMT, reduced cell proliferation, invasion and migration in CRC cells. Interestingly, Slug and Vimentin expression in cancer tissues was significantly higher in patients with higher T stage, lymph node involvement, liver metastasis and advanced tumor node metastasis stages. A significant correlation was observed between Slug and Vimentin expression in CRC (messenger RNA: ρ = 0.546, protein: ρ = 0.405), and increased expression of Slug and Vimentin was significantly associated with poor prognosis. Furthermore, increased expression of Slug emerged as an independent prognostic factor and a predictive marker of lymph node metastasis in CRC patients. Our data provide novel evidence for the biological and clinical significance of Slug and Vimentin expression as potential predictive biomarkers for identifying patients with lymph node metastasis or poor prognosis in CRC.
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Affiliation(s)
- Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan and
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3
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Cyclophosphamide promotes pulmonary metastasis on mouse lung adenocarcinoma. Clin Exp Metastasis 2008; 25:855-64. [PMID: 18766303 DOI: 10.1007/s10585-008-9201-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2008] [Accepted: 07/30/2008] [Indexed: 10/21/2022]
Abstract
Cyclophosphamide (CTX), as a common use of chemotherapeutic agent, has some side effects in clinical treatment. In our experiments, we studied CTX-treated T739 mice using histopathology, immunohistochemistry, reverse transcription polymerase chain reaction and Western blot for markers of proliferation, angiogenesis, tumor progression and distant metastasis. As a result, CTX increased the number and area of metastases and tumor embolus in lungs by effecting on the expression of matrix metalloproteinase-2, intercellular adhesion molecule-1 and tissue inhibitor of metalloproteinase-2. Taken together, it indicated that CTX enhanced the process of pulmonary metastasis by the synergistic effect of matrix-degrading proteases and adhesion proteins.
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Lyons AJ, Jones J. Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Int J Oral Maxillofac Surg 2007; 36:671-9. [PMID: 17643963 DOI: 10.1016/j.ijom.2007.04.002] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2006] [Revised: 03/18/2007] [Accepted: 04/18/2007] [Indexed: 10/23/2022]
Abstract
Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells to form metastases at distant sites. These processes require alterations in cell-cell and cell-extracellular matrix interactions. As cell adhesion molecules play a role in cell-cell and cell-extracellular matrix adhesion and interactions they are involved in the process of tumour invasion and metastases. In epithelial tissues, receptors of the integrin family mediate adhesion to the adjacent matrix whereas cadherins largely mediate intercellular adhesion. These and other cell adhesion molecules such as intercellular adhesion molecule-1, CD44, dystroglycans and selectins, are involved and undergo changes in carcinomas, which provide possible targets for anti-cancer drug treatments. In the extracellular matrix that is associated with tumours, laminin 5, oncofetal fibronectin and tenascin C appear. The degree of expression of some of these moieties indicates prognosis in oral cancer and offer targets for antibody-directed radiotherapy. Metalloproteases which degrade the extracellular matrix are increased in carcinomas, and their activity is necessary for tumour angiogenesis and consequent invasion and metastases. Metalloprotease inhibitors have begun to produce decreases in mortality in clinical trials. This report provides a brief overview of our current understanding of cell adhesion molecules, the extracellular matrix, tumour invasion and metastasis.
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Affiliation(s)
- A J Lyons
- Department of Oral & Maxillofacial Surgery, Guy's Hospital, London SE1 9RT, UK
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Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M. Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res 2007; 13:2082-90. [PMID: 17404090 DOI: 10.1158/1078-0432.ccr-06-2191] [Citation(s) in RCA: 289] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE Myofibroblasts, which are specifically differentiated fibroblasts, are thought to play a central role in the desmoplastic reaction, a dynamic stromal change closely associated with cancer development. Although fundamental studies suggest that myofibroblasts may either facilitate or inhibit cancer progression, cumulative evidence supports their role in promoting tumor progression. The aim of this study was to assess the value of myofibroblasts in the cancer stroma as an indicator of disease recurrence after colorectal cancer surgery. EXPERIMENTAL DESIGN Using computer-assisted image analysis, we quantified myofibroblasts in the cancer-associated stroma of 192 colorectal cancers using alpha-smooth muscle actin as a marker. RESULTS The cancer-associated stroma contained various numbers of myofibroblasts (0.35-19.0%; mean, 5.55 +/- 3.85%). Tumors with abundant myofibroblasts were associated with shorter disease-free survival rate (P = 0.001) for stage II and III colorectal cancer. Multivariate analysis indicated that alpha-smooth muscle actin was a significant prognostic factor comparable with lymph node metastasis and superior to other tumor and stromal components, including histology of the tumor invasive front, peritumoral lymphocytic infiltration, and Crohn's-like lymphoid reaction. Moreover, colorectal cancers with synchronous liver metastasis generally displayed an active desmoplastic reaction, which was retained in the metastatic lesion to a similar extent. CONCLUSIONS The results suggest that the abundance of myofibroblasts in cancer-associated stroma may be a useful indicator of disease recurrence after curative colorectal cancer surgery.
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Affiliation(s)
- Tadashi Tsujino
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, School of Allied Health Science, Faculty of Medicine, Osaka University, Osaka, Japan
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6
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Ngan CY, Yamamoto H, Seshimo I, Tsujino T, Man-i M, Ikeda JI, Konishi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M. Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer. Br J Cancer 2007; 96:986-92. [PMID: 17325702 PMCID: PMC2360104 DOI: 10.1038/sj.bjc.6603651] [Citation(s) in RCA: 115] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Recent studies have identified vimentin, a type III intermediate filament, among genes differentially expressed in tumours with more invasive features, suggesting an association between vimentin and tumour progression. The aim of this study, was to investigate whether vimentin expression in colon cancer tissue is of clinical relevance. We performed immunostaining in 142 colorectal cancer (CRC) samples and quantified the amount of vimentin expression using computer-assisted image analysis. Vimentin expression in the tumour stroma of CRC was associated with shorter survival. Overall survival in the high vimentin expression group was 71.2% compared with 90.4% in the low-expression group (P=0.002), whereas disease-free survival for the high-expression group was 62.7% compared with 86.7% for the low-expression group (P=0.001). Furthermore, the prognostic power of vimentin for disease recurrence was maintained in both stage II and III CRC. Multivariate analysis suggested that vimentin was a better prognostic indicator for disease recurrence (risk ratio=3.5) than the widely used lymph node status (risk ratio=2.2). Vimentin expression in the tumour stroma may reflect a higher malignant potential of the tumour and may be a useful predictive marker for disease recurrence in CRC patients.
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Affiliation(s)
- C Y Ngan
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - H Yamamoto
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita city, Osaka 565-0871, Japan; E-mail:
| | - I Seshimo
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - T Tsujino
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - M Man-i
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - J-I Ikeda
- Department of Pathology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - K Konishi
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - I Takemasa
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - M Ikeda
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - M Sekimoto
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - N Matsuura
- Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University, Osaka 565-0871, Japan
| | - M Monden
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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Terman DS, Bohach G, Vandenesch F, Etienne J, Lina G, Sahn SA. Staphylococcal superantigens of the enterotoxin gene cluster (egc) for treatment of stage IIIb non-small cell lung cancer with pleural effusion. Clin Chest Med 2006; 27:321-34. [PMID: 16716821 DOI: 10.1016/j.ccm.2006.01.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
There has been renewed interest in the superantigens as antitumor agents with the discovery of a group of bacterial superantigens known as the enterotoxin gene cluster (egc staphylococcal enterotoxins [SEs]). This article discusses the mechanisms by which egc SEs induce tumor killing and pleurodesis. The application of SE homolog and nucleic acid compositions as vaccines and for treatment of established tumors is reviewed. Finally, the use of native SEs ex vivo-intratumorally and intravesicularly administered superantigens against established tumors-is described and the interrelation between superantigen therapy and chemoradiotherapy.
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8
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Maruo Y, Gochi A, Kaihara A, Shimamura H, Yamada T, Tanaka N, Orita K. ICAM-1 expression and the soluble ICAM-1 level for evaluating the metastatic potential of gastric cancer. Int J Cancer 2002; 100:486-90. [PMID: 12115535 DOI: 10.1002/ijc.10514] [Citation(s) in RCA: 87] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
ICAM-1 plays an important role in cell-cell and cell-extracellular matrix interactions, especially tumor invasion and cytotoxicity of lymphocytes. In the present study, the relationship between metastasis of gastric cancer and ICAM-1 expression by cancer cells or the serum level of s-ICAM-1 was (s-ICAM-1) was examined. ICAM-1 was detected by immunohistochemic staining in 49.0% of 108 patients with gastric cancer. The ICAM-1 expression rate was higher at a more advanced stage, based on lymph node metastasis, being 46.9% in node-negative and 56.1% in node-positive cases. In patients with liver metastasis, the rate was 90.9%, while it was 43.3% in patients without liver metastasis (p < 0.05). The serum s-ICAM-1 level was 262.1 ng/ml (median 205.5, range 176.0-271.0) in healthy subjects and 391.5 ng/ml (median 317.5, range 148.7-1,768.0) in gastric cancer patients (p < 0.001). The serum s-ICAM-1 level was significantly higher in patients with liver metastasis than in patients without liver metastasis (p < 0.0001). In addition, positive ICAM-1 expression cases had significantly higher s-ICAM-1 levels than negative ones, 408.9 +/- 188.4 and 308.1 +/- 88.1 ng/ml, respectively. These results suggested that ICAM-1 was overexpressed in cancer cells and released as s-ICAM-1, which would promote hematogenous metastasis by suppressing local anticancer immunity.
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Affiliation(s)
- Yukinobu Maruo
- First Department of Surgery, Okayama University Medical School, Okayama, Japan
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Thomas GJ, Speight PM. Cell adhesion molecules and oral cancer. CRITICAL REVIEWS IN ORAL BIOLOGY AND MEDICINE : AN OFFICIAL PUBLICATION OF THE AMERICAN ASSOCIATION OF ORAL BIOLOGISTS 2002; 12:479-98. [PMID: 11806518 DOI: 10.1177/10454411010120060301] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Cell adhesion molecules (CAMs) are found on the surfaces of all cells, where they bind to extracellular matrix molecules or to receptors on other cells. As well as having a structural role, CAMs function as signaling receptors, transducing signals initiated by cellular interactions which regulate many diverse processes, including cell division, migration, and differentiation. Cell adhesion molecules are essential for maintaining stable tissue structure. However, cell adhesion must be dynamic to facilitate the mobility and turnover of cells. In dynamic situations, cells alter their cell-cell and cell-matrix interactions by virtue of altered expression and function of CAMs. The expression of CAMs is normally tightly regulated, thereby controlling cell proliferation, mobility, differentiation, and survival. Many of these processes are misregulated in malignant tumors, and it has been shown that many of the characteristics of tumor cells are attributable to the aberrant expression or function of CAMs. Integrins and E-cadherin are the most important CAMs expressed by stratified squamous epithelium. Altered expression of these molecules has been found in oral carcinoma, where loss of CAM expression is often seen in poorly differentiated lesions. However, up-regulation of certain integrins, such as alphavbeta6, has consistently been found in oral cancer, suggesting that it may play an active role in disease progression.
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Affiliation(s)
- G J Thomas
- Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, University College London, UK
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Madhavan M, Srinivas P, Abraham E, Ahmed I, Vijayalekshmi NR, Balaram P. Down regulation of endothelial adhesion molecules in node positive breast cancer: possible failure of host defence mechanism. Pathol Oncol Res 2002; 8:125-8. [PMID: 12172576 DOI: 10.1007/bf03033721] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Endothelial cell adhesion molecules (CAMs) are important in tumorigenesis and host defense mechanism. Their status in breast cancer with regard to nodal invasion is not yet known. Hence we looked at the expression of three important CAMs: VCAM, ICAM and E-selectin. A downregulation of all these CAMs was noted in node positive breast cancer in comparison to node negative cases. This suggests shedding of these molecules in cases with nodal metastasis which might help the tumor cells to escape the host defense mechanism. On multi-variate analysis, VCAM alone emerged as an independent predictor of nodal metastasis.
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Affiliation(s)
- Maya Madhavan
- Division of Cancer Research, Regional Cancer Centre, Trivandrum, 695011, India.
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11
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Arnold JM, Cummings M, Purdie D, Chenevix-Trench G. Reduced expression of intercellular adhesion molecule-1 in ovarian adenocarcinomas. Br J Cancer 2001; 85:1351-8. [PMID: 11720474 PMCID: PMC2375262 DOI: 10.1054/bjoc.2001.2075] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Ovarian adenocarcinomas develop as the result of multiple genetic and epigenetic changes in the precursor ovarian surface epithelial (OSE) cells which result in a malignant phenotype. We investigated changes in gene expression in ovarian adenocarcinoma using a cDNA array containing 588 known human genes. We found that intercellular adhesion molecule-1 (ICAM-1) was expressed at lower levels in the ovarian tumour cell lines OAW42, PEO1 and JAM than in the immortalised human ovarian surface epithelial cell line HOSE 17.1. Further investigation revealed ICAM-1 was expressed in the surface epithelium of normal ovaries and both mRNA and protein expression levels were reduced in the majority of ovarian adenocarcinoma cell lines and primary tumours. ICAM-1 expression was increased in 8/8 cell lines treated with the de novo methyltransferase inhibitor 5-aza-2'-deoxycytidine, indicating that methylation of CpG islands may play a role in the down-regulation of its expression in primary tumours. There was a significant association between patients whose tumours expressed ICAM-1 and survival (P = 0.03), suggesting that expression levels of ICAM-1 may have clinical relevance.
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Affiliation(s)
- J M Arnold
- The Queensland Institute of Medical Research, PO Box Royal Brisbane Hospital, Herston, Queensland, 4006, Australia
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12
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Xu J, Mei MH, Zeng SE, Shi QF, Liu YM, Qin LL. Expressions of ICAM-1 and its mRNA in sera and tissues of patients with hepatocellular carcinoma. World J Gastroenterol 2001; 7:120-5. [PMID: 11819746 PMCID: PMC4688687 DOI: 10.3748/wjg.v7.i1.120] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- J Xu
- 95 Leque Road, Department of Hepatobiliary Surgery, Guilin Medical College, Guilin 541001, Guangxi, China.
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13
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Mei MH, Xu J, Shi QF, Yang JH, Chen Q, Qin LL. Clinical significance of serum intercellular adhesion molecule-1 detection in patients with hepatocellular carcinoma. World J Gastroenterol 2000; 6:408-410. [PMID: 11819611 PMCID: PMC4688765 DOI: 10.3748/wjg.v6.i3.408] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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14
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Cheng YA, Tsai CC. Nicotine- and arecoline-induced interleukin-1 secretion and intercellular adhesion molecular-1 expression in human oral epidermoid carcinoma cells in vitro. Arch Oral Biol 1999; 44:843-51. [PMID: 10530917 DOI: 10.1016/s0003-9969(99)00073-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The purpose was to examine interleukin (IL)-1 concentrations and intercellular adhesion molecule (ICAM)-1 expression in nicotine/arecoline-exposed oral KB CCL17 cultures. Enzyme-linked immunosorbent assay was used to quantify IL-1 concentrations in culture supernatants. A repeated-measures analysis of variance was used to identify differences among the groups. IL-1 beta concentrations increased by 2.6, 2.7 and 7.5 times those of the control in groups treated with 1 microM nicotine, arecoline or with both, respectively. IL-1 beta concentrations were more dramatically increased when the agents tested were at 100 microM concentration. Similar, although less dramatic, alterations in IL-1 alpha concentrations were observed. The fluorescence intensity of ICAM-1 (CD54) analysed by flow cytometry was also significantly increased in a dose-dependent manner when the cells were treated with nicotine and/or arecoline. Nicotine and arecoline therefore significantly increased IL-1 alpha and -1 beta secretions and the surface expression of ICAM-1 in KB CCL17 cells.
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Affiliation(s)
- Y A Cheng
- Graduate Institute of Dental Sciences, Kaohsiung Medical College, Taiwan, Republic of China
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15
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Pelliccia P, Natoli C, Petitti MT, Verrotti A, Chiarelli F, Iacobelli S. Elevated levels of circulating immunostimulatory 90K in Henoch-Schoenlein purpura. J Clin Immunol 1999; 19:143-7. [PMID: 10226889 DOI: 10.1023/a:1020562702083] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
In order to clarify the immunologic reaction present in Henoch-Schoenlein purpura (HSP), 20 children (11 boys and 9 girls; median age, 5.8 +/- 2.8 years) with HSP and 20 sex- and age-matched healthy children were studied. The 90K/Mac-2 BP serum concentrations were significantly higher in the patients than in the healthy controls (12.5 +/- 7.5 vs 4.5 +/- 2.7 micrograms/ml, respectively; P < 0.0001). 90K/Mac-2 BP values higher than the cutoff value were observed in 13 of 20 (65%) patient. The soluble intercellular adhesion molecule 1 concentrations were significantly higher in HSP patients than controls (P < 0.0001), with mean values of 1631 +/- 703 and 85 +/- 16 ng/ml, respectively. The 90K/Mac-2 BP serum levels were significantly correlated with soluble intercellular adhesion molecule 1 (r = 0.90, P < 0.0001). Although the underlying causes of these immunological abnormalities are unclear, these observations suggest that the 90K/Mac-2 BP protein may play a role in the immunological reactions involved in the development of HSP.
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Affiliation(s)
- P Pelliccia
- Department of Medicine, University of Chieti, Italy
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16
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Maurer CA, Friess H, Kretschmann B, Wildi S, Müller C, Graber H, Schilling M, Büchler MW. Over-expression of ICAM-1, VCAM-1 and ELAM-1 might influence tumor progression in colorectal cancer. Int J Cancer 1998; 79:76-81. [PMID: 9495363 DOI: 10.1002/(sici)1097-0215(19980220)79:1<76::aid-ijc15>3.0.co;2-f] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Adhesion molecules might play a role in tumor progression. We investigated expression of the adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in 24 primary colorectal carcinomas using immuno-histochemistry and Northern blot analysis. Normal colonic tissue from the same patients served as controls. ICAM-1 immunostaining was restricted to the intercellular matrix and vascular endothelial cells. The vast majority of normal tissue samples revealed only faint ICAM-1 immunoreactivity. However, moderate to strong immunostaining was found in 86% of cancerous sections. The ICAM-1 immunoreaction was more intense in well-differentiated carcinomas as well as in the adenomatous parts and transition zones of cancers. Similarly, the cancers exhibited markedly enhanced VCAM-1 and ELAM-1 immunostaining in the endothelial cells of small blood vessels. The intense vascular immunostaining by ICAM-1 and VCAM-1 was associated with a strong presence of CD3-positive T lymphocytes, whereas ELAM-1 immunoreactivity did not correlate with round cell infiltration. On Northern blot analysis, ICAM-1, VCAM-1 and ELAM-1 mRNA levels were increased in 67%, 57% and 63% of carcinomas, respectively, in comparison with normal tissue samples. Densitometric analysis of Northern blots revealed an increase in ICAM-1 by 2.1-fold, an increase in VCAM-1 by 3.4-fold and an increase in ELAM-1 by 2.2-fold in cancerous tissues compared to normal controls. Over-expression of ICAM-I might prevent cell-cell disruption and, hence, tumor dissemination. Furthermore, over-expression of ICAM-1 and VCAM-1, but not ELAM-1, might favor host anti-tumor defense by trafficking of lymphocytes.
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Affiliation(s)
- C A Maurer
- Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland
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Nasu K, Narahara H, Etoh Y, Kawano Y, Hirota Y, Miyakawa I. Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and the expression of ICAM-1 mRNA in uterine cervical cancer. Gynecol Oncol 1997; 65:304-8. [PMID: 9159342 DOI: 10.1006/gyno.1997.4636] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The purpose of this investigation was to evaluate the serum level of soluble intercellular adhesion molecule-1 (sICAM-1) in patients with squamous cell carcinoma of the cervix. Serum levels of sICAM-1 were measured by enzyme-linked immunosorbent assay in patients with cervical cancer (stage 0 through IV). Expression of mRNA in tumor tissues was evaluated by reverse transcriptase-polymerase chain reaction. Serum level of sICAM-1 in patients with advanced-stage (II-IV) or recurrent cervical cancer was found to be increased significantly. Expression of ICAM-1 mRNA was observed in most tumor tissues. Results suggest that sICAM-1 is shed from the cancerous tissue in patients with squamous cell carcinoma of the cervix.
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Affiliation(s)
- K Nasu
- Department of Obstetrics and Gynecology, Oita Medical University, Hasama-machi, Japan
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18
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Tanabe K, Campbell SC, Alexander JP, Steinbach F, Edinger MG, Tubbs RR, Novick AC, Klein EA. Molecular regulation of intercellular adhesion molecule 1 (ICAM-1) expression in renal cell carcinoma. UROLOGICAL RESEARCH 1997; 25:231-8. [PMID: 9286030 DOI: 10.1007/bf00942091] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Intercellular adhesion molecule-1 (ICAM-1) mediates two important functional aspects of tumor biology, namely enhancement of tumor metastasis and mediation of host defense mechanisms such as lymphocyte-mediated tumor cytotoxicity. Since ICAM-1 is expressed by most renal cell carcinomas (RCC), the regulation of ICAM-1 expression is important in understanding the biological behavior of RCC. We report an investigation on ICAM-1 expression and molecular regulation by cytokines and protein kinase C activator on RCC cell lines. Of the various cytokines, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and phorbol myristate acetate (PMA) strongly upregulated ICAM-1 protein expression on RCC. The kinetics of ICAM-1 message induction was studied by Northern analysis of total RNA extracted from RCC and normal kidney proximal tubular (NKPT) cells. Time course studies showed that ICAM-1 mRNA was upregulated by INF gamma, TNF alpha, and PMA, plateaued after 2 h, and remained increased for up to 24 h. Although ICAM-1 mRNA in NKPT cells was upregulated by these cytokines, their messages returned to basal levels after 24 h. ICAM-1 mRNA stability assays showed that both unstimulated and stimulated RCC cells had very stable ICAM-1 mRNA up to 24 h. In order to investigate whether increased gene transcription contributes to ICAM-1 upregulation, RCC cells were treated with TNF alpha, IFN gamma, or PMA with or without simultaneous addition of actinomycin D. ICAM-1 message induction-blocking studies suggested that primary upregulation of ICAM-1 mRNA may be caused by transcriptional upregulation. These results suggest that long-lasting ICAM-1 message upregulation in response to cytokines or PMA may be due to transcriptional upregulation in the early phase and stabilization of ICAM-1 message in the later phase (after 4 h). These observations suggest that RCC may lack the normal downregulatory mechanisms which control ICAM-1 expression and may explain the high frequency of ICAM-1 expression observed on primary human RCC.
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Affiliation(s)
- K Tanabe
- Department of Urology, Tokyo Women's Medical College, Japan
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19
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Abstract
Cell adhesion molecules are glycoproteins expressed on the cell surface and play an important role in inflammatory as well as neoplastic diseases. There are four main groups: the integrin family, the immunoglobulin superfamily, selectins, and cadherins. The integrin family has eight subfamilies, designated as beta 1 through beta 8. The most widely studied subfamilies are beta 1 (CD29, very late activation [VLA] members), beta 2 (leukocyte integrins such as CD11a/CD18, CD11b/CD18, CD11c/CD18, and alpha d beta 2), beta 3 (CD61, cytoadhesions), and beta 7 (alpha 4 beta 7 and alpha E beta 7). The immunoglobulin superfamily includes leukocyte function antigen-2 (LFA-2 or CD2), leukocyte function antigen-3 (LFA-3 or CD58), intercellular adhesion molecules (ICAMs), vascular adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PE-CAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The selectin family includes E-selectin (CD62E), P-selectin (CD62P), and L-selectin (CD62L). Cadherins are major cell-cell adhesion molecules and include epithelial (E), placental (P), and neural (N) subclasses. The binding sites (ligands/receptors) are different for each of these cell adhesion molecules (e.g., ICAM binds to CD11/CD18; VCAM-1 binds to VLA-4). The specific cell adhesion molecules and their ligands that may be involved in pathologic conditions and potential therapeutic strategies by modulating the expression of these molecules will be discussed.
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Affiliation(s)
- C S Elangbam
- Department of Pathology, WIL Research Laboratories, Ashland, OH, USA
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20
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Osaki T, Mitsudomi T, Yoshida Y, Oyama T, Ohgami A, Nakanishi K, Nakanishi R, Sugio K, Yasumoto K. Increased levels of serum intercellular adhesion molecule-1 (ICAM-1) in patients with non-small cell lung cancer. Surg Oncol 1996; 5:107-13. [PMID: 8908715 DOI: 10.1016/s0960-7404(96)80009-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Serum concentrations of soluble ICAM-1 were measured by an enzyme-linked immunosorbent assay in 80 patients with non-small cell lung cancer (NSCLC). The mean serum concentration of soluble ICAM-1 in 80 patients with NSCLC was 472.8 +/- 370.8 ng ml-1 (range 75.6-3177.4 ng ml-1), whereas it was 196.8 +/- 54.6 ng ml-1 (range 128.1-276.4 ng ml-1) in 10 healthy controls. Sixty of 80 patients with NSCLC (75.0%) showed elevated concentrations (more than 306 ng ml-1, mean+2 SD in controls). The differences in mean serum concentration and positive rate between control subjects and NSCLC patients were significant (P = 0.0001). Serum ICAM-1 concentrations showed a significantly positive correlation with primary tumour size (maximum diameter) (P = 0.0209). Although the difference was not significant, the overall survival of patients with low serum ICAM-1 concentrations (< 306 ng ml-1) tended to be longer than that of patients with high concentrations (> or = 306 ng ml-1). These results suggest that serum ICAM-1 may be useful for serological diagnosis, monitoring of tumour volume or quantity in patients with NSCLC.
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Affiliation(s)
- T Osaki
- Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
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21
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Abstract
The prominent desmoplastic or stromal reaction seen in many invasive carcinomas suggests that stromal cells play a role in cancer pathogenesis. Investigations based on cell typing, using antibodies to cytoskeletal constituents, have revealed that most tumors contain various types of fibroblasts. Stromal cells with myofibroblastic differentiation features are the predominant cell type at the periphery of epithelial tumors. These tumor-activated fibroblasts play a major role in tumor development and spread, affecting the proliferation, differentiation, invasion or regression of cancer cells. This review considers the events inducing the different fibroblastic responses and the role of tumor-activated fibroblasts in both tumor development and anti-cancer treatments.
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Affiliation(s)
- M Grégoire
- Institut de Biologie, INSERM U419, Nantes, France
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22
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Mizoi T, Ohtani H, Suzuki Y, Shiiba K, Matsuno S, Nagura H. Intercellular adhesion molecule-1 expression by macrophages in human gastrointestinal carcinoma: possible roles as host immune/inflammatory reaction. Pathol Int 1995; 45:565-72. [PMID: 7496501 DOI: 10.1111/j.1440-1827.1995.tb03504.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Tumor-associated macrophages (TAM) are one of the factors which modulate the carcinoma progression. The present study described immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in stromal cells in human gastrointestinal carcinoma identifying the cell types by immunoelectron microscopy. In colon and gastric carcinomas, ICAM-1-positive cells were mostly stromal cells, and major cell types were identified as macrophages and fibroblasts by immunoelectron microscopy. Macrophages were characterized by their ovoid shape, cytoplasmic projections, abundant vacuoles, phagocytosis, and paucity of rough endoplasmic reticulum. Fibroblasts contained stacks of rough endoplasmic reticulum. Macrophages were major cells among ICAM-1-positive cells along the invasive margin, while fibroblasts were predominant in the stroma within carcinoma in colon and intestinal-type gastric carcinomas. Lymphocytes positive for lymphocyte function associated antigen (LFA-1), a counter-receptor of ICAM-1, were densely distributed along the invasive margin, and sparsely in the stroma within carcinoma. In diffuse-type gastric carcinoma, most macrophages were dendritic-shaped and negative for ICAM-1. Our study suggests that the invasive margin is an area similar to active inflammation, where the antigen presenting cells (macrophages) and lymphocytes may interact via the ICAM-1/LFA-1 adhesion.
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Affiliation(s)
- T Mizoi
- Department of Pathology, Tohoku University, School of Medicine, Sendai, Japan
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23
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Vogetseder W, Denner J, Boller K, Kurth R, Dierich MP. Human endogenous retrovirus K does not encode mouse mammary tumor virus-related antigens in human breast carcinomas. AIDS Res Hum Retroviruses 1995; 11:869-72. [PMID: 7546915 DOI: 10.1089/aid.1995.11.869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Affiliation(s)
- W Vogetseder
- Institut für Hygiene, Leopold Franzens Universität, Innsbruck, Austria
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24
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Rockett JC, Darnton SJ, Crocker J, Matthews HR, Morris AG. Expression of HLA-ABC, HLA-DR and intercellular adhesion molecule-1 in oesophageal carcinoma. J Clin Pathol 1995; 48:539-44. [PMID: 7665697 PMCID: PMC502684 DOI: 10.1136/jcp.48.6.539] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
AIM To examine the expression of HLA-ABC and HLA-DR major histocompatibility (MHC) antigens and intercellular adhesion molecule (ICAM)-1 in normal, inflamed, metaplastic, and neoplastic oesophageal tissue and in freshly disaggregated tumours. METHODS Sequential sections of frozen tissue and cytospins of freshly disaggregated tumour were stained using the ABC peroxidase system and monoclonal antibodies specific for HLA-ABC, HLA-DR and ICAM-1. RESULTS Normal oesophageal tissue showed positive staining for HLA-ABC in the basal layers of the oesophageal squamous epithelium and on the epithelial cells of the submucosal oesophageal glands. HLA-DR and ICAM-1 were not detected in either of these cell types. In 20 of 37 (54%) carcinomas HLA-ABC was expressed weakly, with heterogeneous expression in nine (24%). Two tumours showed strong expression of HLA-ABC, but 15 of 37 (41%) were negative. HLA-DR and ICAM-1 were expressed weakly in six of 37 (16%) carcinomas without correlation with each other or with the expression of HLA-ABC. CONCLUSIONS HLA-ABC is absent from a high proportion of oesophageal carcinomas (41%) and is otherwise variably and weakly expressed with strong expression in only a small fraction (3%). In other carcinomas there is a higher level of HLA-ABC expression. This discrepancy may partly explain the aggressive nature of oesophageal carcinomas. HLA-DR and ICAM-1 are not normally expressed on those cells from which oesophageal carcinomas are thought to arise. The limited expression found here could suggest a partial or inhibited immune response against oesophageal carcinoma. In vivo repressive factors may be involved.
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Affiliation(s)
- J C Rockett
- Department of Biological Sciences, University of Warwick, Coventry
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25
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Jahnke A, Stolpe A, Caldenhoven E, Johnson JP. Constitutive Expression of Human Intercellular Adhesion Molecule-1 (ICAM-1) is Regulated by Differentially Active Enhancing and Silencing Elements. ACTA ACUST UNITED AC 1995. [DOI: 10.1111/j.1432-1033.1995.00439.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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26
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Kroesen BJ, Buter J, Sleijfer DT, Janssen RA, van der Graaf WT, The TH, de Leij L, Mulder NH. Phase I study of intravenously applied bispecific antibody in renal cell cancer patients receiving subcutaneous interleukin 2. Br J Cancer 1994; 70:652-61. [PMID: 7917912 PMCID: PMC2033411 DOI: 10.1038/bjc.1994.366] [Citation(s) in RCA: 56] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
In a phase I trial the toxicity and immunomodulatory effects of combined treatment with intravenous (i.v.) bispecific monoclonal antibody BIS-1 and subcutaneous (s.c.) interleukin 2 (IL-2) was studied in renal cell cancer patients. BIS-1 combines a specificity against CD3 on T lymphocytes with a specificity against a 40 kDa pancarcinoma-associated antigen, EGP-2. Patients received BIS-1 F(ab')2 fragments intravenously at doses of 1, 3 and 5 micrograms kg-1 body weight during a concomitantly given standard s.c. IL-2 treatment. For each dose, four patients were treated with a 2 h BIS-1 infusion in the second and fourth week of IL-2 therapy. Acute BIS-1 F(ab')2-related toxicity with symptoms of chills, peripheral vasoconstriction and temporary dyspnoea was observed in 2/4 and 5/5 patients at the 3 and 5 micrograms kg-1 dose level respectively. The maximum tolerated dose (MTD) of BIS-1 F(ab')2 was 5 micrograms kg-1. Elevated plasma levels of tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were detected at the MTD. Flow cytometric analysis showed a dose-dependent binding of BIS-1 F(ab')2 to circulating T lymphocytes. Peripheral blood mononuclear cells (PBMCs), isolated after treatment with 3 and 5 micrograms kg-1 BIS-1, showed increased specific cytolytic capacity against EGP-2+ tumour cells as tested in an ex vivo performed assay. Maximal killing capacity of the PBMCs, as assessed by adding excess BIS-1 to the assay, was shown to be decreased after BIS-1 infusion at 5 micrograms kg-1 BIS-1 F(ab')2. A BIS-1 F(ab')2 dose-dependent disappearance of circulating mononuclear cells from the peripheral blood was observed. Within the circulating CD3+ CD8+ lymphocyte population. LFA-1 alpha-bright and HLA-DR+ T-cell numbers decreased preferentially. It is concluded that i.v. BIS-1 F(ab')2, when combined with s.c. IL-2, has a MTD of 5 micrograms kg-1. The treatment endows the T lymphocytes with a specific anti-EGP-2-directed cytotoxic potential.
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MESH Headings
- Adjuvants, Immunologic/administration & dosage
- Adjuvants, Immunologic/adverse effects
- Aged
- Antibodies, Bispecific/administration & dosage
- Antibodies, Bispecific/adverse effects
- Antibodies, Bispecific/metabolism
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- CD3 Complex/immunology
- Carcinoma, Renal Cell/immunology
- Carcinoma, Renal Cell/therapy
- Dose-Response Relationship, Drug
- Feasibility Studies
- Female
- Humans
- Immunoglobulin Fragments/administration & dosage
- Immunoglobulin Fragments/adverse effects
- Immunoglobulin Fragments/metabolism
- Immunophenotyping
- Infusions, Intravenous
- Injections, Subcutaneous
- Interferon-gamma/biosynthesis
- Interferon-gamma/blood
- Interferon-gamma/metabolism
- Interleukin-2/administration & dosage
- Interleukin-2/adverse effects
- Kidney Neoplasms/immunology
- Kidney Neoplasms/therapy
- Leukocyte Count/drug effects
- Male
- Middle Aged
- T-Lymphocytes/immunology
- T-Lymphocytes/metabolism
- Tumor Necrosis Factor-alpha/biosynthesis
- Tumor Necrosis Factor-alpha/metabolism
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Affiliation(s)
- B J Kroesen
- University Hospital Groningen, Department of Clinical Immunology, The Netherlands
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27
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Campbell SC, Tanabe K, Alexander JP, Edinger M, Tubbs RR, Klein EA. Intercellular adhesion molecule-1 expression by bladder cancer cells: functional effects. J Urol 1994; 151:1385-90. [PMID: 7908992 DOI: 10.1016/s0022-5347(17)35265-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The role of intercellular adhesion molecule-1 (ICAM-1) and its ligand, leukocyte function-associated antigen-1 (LFA-1), in the interaction between bladder cancer cells and lymphokine activated killer (LAK) cells was investigated. Expression and modulation of ICAM-1 by cytokine treatment was assessed by immunocytometry and Northern blot analysis. Four of five human bladder cancer cell lines expressed ICAM-1 constitutively and responded to cytokine stimulation. Expression of ICAM-1 was upregulated most consistently by treatment with interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha), cytokines that are released into the urine after intravesical BCG treatment. In contrast, interleukin-1 and phorbol myristate acetate exhibited variable effects on ICAM-1 expression, and interferon-alpha had no effect. The adherence of LAK cells to bladder cancer cell monolayers and LAK cell-mediated cytolysis were then studied. Monoclonal antibodies to ICAM-1 and LFA-1 significantly decreased the binding of LAK cells to the cell lines that express ICAM-1 (37 to 75% reduction, p < 0.05), and cytokine treatment (IFN gamma, TNF alpha) of these cells enhanced ICAM-1 dependent adherence (18 to 39% increase, p < 0.05). In contrast, these manipulations had no effect on the binding of LAK cells to the UMUC3 cell line, which does not express ICAM-1. Monoclonal antibodies to LFA-1 decreased LAK cell mediated cytolysis of the bladder cancer cells from 27 to 65% (p < 0.05), but anti-ICAM-1 antibodies were much less effective (0 to 25% decrease in cytolysis). Cytokine treatment (IFN gamma, TNF alpha) of the tumor cells did not significantly increase LAK cell-mediated cytolysis, despite upregulation of ICAM-1. These data demonstrate that ICAM-1 plays a role in the binding of LAK cells to bladder cancer cells but is only marginally involved in the process of LAK cell-mediated cytolysis. These findings suggest that adhesion molecules may be important mediators of the immune response to bladder cancer after intravesical BCG therapy.
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Affiliation(s)
- S C Campbell
- Department of Urology, Cleveland Clinic Foundation, Ohio 44195
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28
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Giavazzi R, Nicoletti MI, Chirivi RG, Hemingway I, Bernasconi S, Allavena P, Gearing AJ. Soluble intercellular adhesion molecule-1 (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumour xenografts. Eur J Cancer 1994; 30A:1865-70. [PMID: 7880619 DOI: 10.1016/0959-8049(94)00345-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
We have demonstrated that patients with ovarian carcinoma have higher levels of soluble intercellular adhesion molecule-1 (ICAM-1) in their serum and ascitic fluids than serum from normal individuals and non-neoplastic gynaecological disease or ascites from patients with cirrhosis. In order to investigate the source of the ICAM-1, and to study the mechanisms which regulate ICAM-1 release in ovarian carcinoma, we have employed the nude mouse model system. Three different human ovarian carcinoma (HOC) cell lines were grown as ascitic tumours in the peritoneal cavity of nude mice. HOC xenografts harvested from nude mice expressed comparable levels of ICAM-1 on their cell surface. Human ICAM-1 was detected, with a species-specific ELISA, in serum and ascitic fluid of tumour-bearing mice, confirming that the tumours were the source of the ICAM-1. The three HOC xenografts showed different levels of ICAM-1 release, but within each xenograft model the level of ICAM-1 in serum and ascitic fluid correlated with the tumour burden. The level of ICAM-1 released by the HOC xenografts could be increased by in vivo treatment with interferon gamma (IFN-gamma). Interleukin 1 (IL-1), tumour necrosis factor (TNF) and IFN gamma increased the cell surface expression of ICAM-1 and caused the release of soluble ICAM-1 from HOC cells established in vitro. The nude mouse provides a useful system in which to study the effects of modulating ICAM-1 release on the progression of ovarian carcinoma and suggests that measuring ICAM-1 levels in the blood or ascites of patients may provide an indication of tumour burden.
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Affiliation(s)
- R Giavazzi
- Istituto di Ricerche Farmacologiche Mario Negri, Bergamo
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29
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Maemura M, Dickson RB. Are cellular adhesion molecules involved in the metastasis of breast cancer? Breast Cancer Res Treat 1994; 32:239-60. [PMID: 7865853 DOI: 10.1007/bf00666002] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- M Maemura
- Lombardi Cancer Research Center, Georgetown University, Washington, DC 20007
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30
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Dippold W, Wittig B, Schwaeble W, Mayet W, Meyer zum Büschenfelde KH. Expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in colonic epithelial cells. Gut 1993; 34:1593-7. [PMID: 7902311 PMCID: PMC1374428 DOI: 10.1136/gut.34.11.1593] [Citation(s) in RCA: 84] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The expression of intercellular adhesion molecule-1 (ICAM-1, CD54) was examined in 16 surgically removed colonic tumours and two colonic carcinoma cell lines. Immunohistochemistry showed a varying percentage of ICAM-1 positive colonic carcinoma cells in 9/16 tissue specimens, while normal colonic tissue (apart from a slight reactivity of endothelial cells) was not stained. The presence of the ICAM-1 molecule on the cell surface and the expression of ICAM-1 mRNA were investigated for two colonic carcinoma cell lines. It was possible to enhance the expression of ICAM-1 considerably by incubating the cells in the presence of inflammatory cytokines in HT-29 and CaCo-2 cells. The responsiveness to either interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha), or interleukin 1 beta (IL-1 beta) treatment was different in each cell line. Interestingly, ICAM-1 is shed by colonic carcinoma cells because soluble sICAM-1 was detected in the cell culture supernatants. In comparison with normal serum samples, the mean value of sICAM-1 in 63 samples of patients with colonic carcinoma and in 20 cases of active inflammatory bowel disease is raised about twofold. It remains to be clarified what part both forms of ICAM-1 play in the course of colonic cancer, ulcerative colitis, and Crohn's disease.
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Affiliation(s)
- W Dippold
- I Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität, Mainz, Germany
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31
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Torii A, Harada A, Nakao A, Nonami T, Ito M, Takagi H. Expression of intercellular adhesion molecule-1 in hepatocellular carcinoma. J Surg Oncol 1993; 53:239-42. [PMID: 8101890 DOI: 10.1002/jso.2930530410] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The expression of intercellular adhesion molecule-1 (ICAM-1) was investigated in frozen sections obtained from 40 resected liver specimens of patients with hepatocellular carcinoma using immunoperoxidase techniques and immunoelectron microscopy. ICAM-1 was expressed in 80% of the HCC specimens on the membrane of cancer cells. In noncancerous regions characterized by cirrhosis in 28 cases and chronic hepatitis in 12 cases, ICAM-1 was rarely expressed on hepatocytes but was expressed mainly on the endothelium of portal vessels and sinusoidal lining cells. These results suggest that expression of ICAM-1 in hepatocellular carcinoma may be induced by malignant transformation of hepatocytes.
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Affiliation(s)
- A Torii
- Department of Surgery II, Nagoya University School of Medicine, Japan
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32
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Bajaj P, Lawry J, Shenton G, Rees RC. Interleukin-6 and tumour necrosis factor alpha synergistically block S-phase cell cycle and upregulate intercellular adhesion molecule-1 expression on MCF7 breast carcinoma cells. Cancer Lett 1993; 71:143-9. [PMID: 8364888 DOI: 10.1016/0304-3835(93)90109-m] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The effect of IL-6 and TNF alpha were studied on human MCF7 breast cancer cells. Synergistic interaction between IL-6 and TNF alpha, on the growth inhibition (50% reduction in the percentage of S-phase cells) and the upregulation of ICAM-1 expression (4 to 11-fold increase) was shown using flow cytometric methods. IL-6 and TNF alpha alone had negligible effect on the cell cycle. The individual effect of IL-6 resulted in down-regulation of ICAM-1 expression (30-35%), while TNF alpha always upregulated ICAM-1 (1.5 to 4-fold increase). The combined effect of IL-6 and TNF alpha consistently caused an increased expression of ICAM-1, which was greater than the sum of each one alone and also sustained for 72 h following cytokine withdrawal.
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Affiliation(s)
- P Bajaj
- Institute for Cancer Studies, University of Sheffield Medical School, UK
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33
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Darley R, Morris A, Passas J, Bateman W. Interactions between interferon gamma and retinoic acid with transforming growth factor beta in the induction of immune recognition molecules. Cancer Immunol Immunother 1993; 37:112-8. [PMID: 8100485 PMCID: PMC11038413 DOI: 10.1007/bf01517043] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/1992] [Accepted: 02/02/1993] [Indexed: 01/28/2023]
Abstract
The cell-surface expression of major histocompatibility (MHC) antigens and the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) is essential for target cell recognition by T lymphocytes. The expression of both classes of molecule is induced by various cytokines, notably interferon gamma (IFN gamma). Since transforming growth factor beta (TGF beta) has been recently reported to antagonise HLA-DR induction by IFN gamma we have examined, using a number of murine and human cell lines, the effect of TGF beta on IFN gamma-induced MHC class I and class II and ICAM-1 expression. All of the cell lines tested expressed elevated class I MHC following IFN gamma treatment. Class II MHC induction was seen on most but not all of the cells, the exceptions being among a panel of human colorectal carcinoma cell lines. A striking difference between cells of different origin was noted in the response to TGF beta. TGF beta was found to antagonise IFN gamma-induced class I and class II MHC expression on C3H 10T1/2 murine fibroblasts, early-passage BALB/c mouse embryo fibroblasts, a murine oligodendroglioma cell line, and on MRC5 human fibroblasts and two human glioblastoma cell lines. Class II MHC was much more strongly inhibited (sometimes completely) than class I MHC. TGF beta also inhibited induction of class I MHC expression by IFN alpha. However, TGF beta did not inhibit class I or class II MHC induction by IFN gamma in any of the nine colorectal carcinoma cell lines, although two of five of the lines tested were growth-inhibited by TGF beta. On the other hand, human ICAM-1 induction by IFN gamma was not affected by simultaneous treatment with TGF beta in any of the cell lines. The down-regulation of IFN gamma-induced MHC antigens by TGF beta is not, therefore, the result of a general antagonism of IFN gamma. Retinoic acid has recently been reported to induce ICAM-1 expression on human tumour cells. We have confirmed this observation on MRC5, and the two human glioblastoma cell lines, however six colorectal carcinoma cell lines tested did not respond. In contrast to IFN gamma-induced ICAM-1 expression, retinoic-acid-induced ICAM-1 expression was inhibited by TGF beta on two of the three responsive lines.
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Affiliation(s)
- R Darley
- Department of Biological Sciences, University of Warwick, Coventry, UK
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Wölfel T, Herr W, Coulie P, Schmitt U, Meyer zum Büschenfelde KH, Knuth A. Lysis of human pancreatic adenocarcinoma cells by autologous HLA-class I-restricted cytolytic T-lymphocyte (CTL) clones. Int J Cancer 1993; 54:636-44. [PMID: 8514455 DOI: 10.1002/ijc.2910540419] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
From the primary site of a pancreatic adenocarcinoma (patient BE) a permanent cell line (MZ-PC-2) was established in tissue culture. In the course of mixed lymphocyte-tumor-cell cultures (MLTC) with autologous blood-derived lymphocytes, we isolated CTL clones that lysed autologous tumor cells but not autologous EBV-transformed B cells (EBV-B) and not K562. Pre-treatment of MZ-PC-2 cells with IFN-gamma was required to obtain significant lysis in 4-hr cytotoxicity assays. IFN-gamma was superior to IFN-alpha in that respect. Among MLTC responder lymphocytes, tumor-reactive CTL proliferated more strongly in response to MZ-PC-2 cells treated with IFN-gamma than to untreated tumor cells. Three CTL clones derived from MLTC were chosen for further analysis. They were CD3+, CD8+, TCR-alpha/beta+ and behaved identically in all functional aspects tested. They all expressed the same TCR-beta chain, indicating that they descended from a common precursor lymphocyte and were directed against the same antigen. According to antibody-inhibition experiments, BE-CTL recognized their targets via an HLA-B molecule carrying the Bw6 supertypic determinant. Irrespective of pre-incubation with IFN-gamma, low levels of tumor-cell lysis, or none, were seen when MZ-PC-2 cells were kept in medium supplemented with autologous serum or serum pooled from healthy volunteers instead of FCS. Lysability was restored when TNF-alpha was added to human serum. Serum-free medium was found to enhance the susceptibility of MZ-PC-2 cells to lysis by autologous CTL.
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MESH Headings
- Adenocarcinoma/immunology
- Adenocarcinoma/pathology
- Adult
- Antibodies, Monoclonal/pharmacology
- Base Sequence
- Histocompatibility Antigens Class I/immunology
- Humans
- Interferon-gamma/pharmacology
- Lymphocyte Culture Test, Mixed
- Molecular Sequence Data
- Pancreatic Neoplasms/immunology
- Pancreatic Neoplasms/pathology
- Receptors, Antigen, T-Cell, alpha-beta/immunology
- Receptors, Antigen, T-Cell, alpha-beta/metabolism
- T-Lymphocytes, Cytotoxic/drug effects
- T-Lymphocytes, Cytotoxic/immunology
- T-Lymphocytes, Cytotoxic/pathology
- Tumor Cells, Cultured/immunology
- Tumor Cells, Cultured/pathology
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Affiliation(s)
- T Wölfel
- I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Germany
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35
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Ohlinger W, Dinges HP, Zatloukal K, Mair S, Gollowitsch F, Denk H. Immunohistochemical detection of tumor necrosis factor-alpha, other cytokines and adhesion molecules in human livers with alcoholic hepatitis. VIRCHOWS ARCHIV. A, PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY 1993; 423:169-76. [PMID: 7694422 DOI: 10.1007/bf01614767] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
This immunohistochemical study was designed to investigate the possible contribution to and topographical distribution of some important cytokines, such as tumour necrosis factor alpha (TNF alpha) and interleukins, in acute alcoholic hepatitis. The well-known inductive capacity of these cytokines with respect to the expression and/or up-regulation of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1), was a further point to be studied. Moreover, the proposed induction of adhesion molecules might also be associated with the activation and attraction of a special population of inflammatory cells characteristic for alcoholic hepatitis. Frozen liver samples from patients who died with signs of acute alcoholic hepatitis were evaluated using the alkaline phosphatase anti-alkaline phosphatase immunostaining technique and also single and double indirect immunofluorescence. In acute alcoholic hepatitis TNF alpha could be detected predominantly in ballooned hepatocytes, which often contained alcoholic hyalin (Mallory bodies). Moreover, TNF alpha showed a co-distribution with ICAM-1 expressed in the membranes of hepatocytes and with the occurrence of CD11b positive polymorphonuclear leukocytes (neutrophils) suggesting a possible major role of the beta 2-integrin Mac-1 as a ligand for ICAM-1. No induction of ELAM-1 could be found. In alcoholic hepatitis cytokines may be responsible for the induction of the adhesion molecule ICAM-1 on hepatocytic membranes and activate a defined population of inflammatory cells, thus contributing to the characteristic histological picture of acute alcoholic hepatitis with its concentration of neutrophils especially in areas with ballooned Mallory body-containing hepatocytes. Our results are in line with clinical findings showing high levels of TNF alpha and interleukin-1 in sera of patients with alcoholic hepatitis and with the already reported expression of ICAM-1 on hepatocytes.
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Affiliation(s)
- W Ohlinger
- Institute of Pathology, University of Graz School of Medicine, Austria
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36
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Seko Y, Matsuda H, Kato K, Hashimoto Y, Yagita H, Okumura K, Yazaki Y. Expression of intercellular adhesion molecule-1 in murine hearts with acute myocarditis caused by coxsackievirus B3. J Clin Invest 1993; 91:1327-36. [PMID: 8097205 PMCID: PMC288103 DOI: 10.1172/jci116333] [Citation(s) in RCA: 84] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
A cell-mediated autoimmune mechanism has been strongly implicated in the pathogenesis of viral myocarditis. Using a murine model of myocarditis caused by coxsackievirus B3 (CVB3), we previously reported that the heart is infiltrated first by natural killer cells, which express a cytolytic factor, perforin, and then by activated T cells. This action may play an important role in the pathogenesis of the observed myocardial cell damage. Cell-cell contact and adhesion is required in immune responses, and intercellular adhesion molecule-1 (ICAM-1), which is a ligand for lymphocyte function-associated antigen-1 (LFA-1), plays an important role in this process. To investigate the essential role of the ICAM-1/LFA-1 pathway in the cell-mediated cytotoxicity involved in viral myocarditis, we examined by immunofluorescence the expression of ICAM-1 in murine hearts with acute myocarditis caused by CVB3. We also evaluated the induction of ICAM-1 in cultured cardiac myocytes treated with cytokines by immunofluorescence and Northern blot hybridization. Furthermore, we analyzed the effects of in vivo administration of anti-ICAM-1 mAbs on the inflammation associated with acute viral myocarditis. We found that CVB3-induced murine acute myocarditis resulted in enhanced expression of ICAM-1 in myocardial cells. The expression of ICAM-1 in myocardial cells could be induced in vitro by IFN-gamma and TNF-alpha, which were shown to be synthesized by the infiltrating cells. In vivo treatment with F(ab')2 fragments of an anti-ICAM-1 mAb significantly reduced the myocardial inflammation induced by CVB3. These data strongly suggest that the expression of ICAM-1 in myocardial cells plays a critical role in the cell-mediated cytotoxicity involved in acute viral myocarditis.
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Affiliation(s)
- Y Seko
- Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
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37
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Tomita Y, Kimura M, Tanikawa T, Nishiyama T, Morishita H, Takeda M, Fujiwara M, Sato S. Immunohistochemical detection of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex class I antigens in seminoma. J Urol 1993; 149:659-63. [PMID: 8094763 DOI: 10.1016/s0022-5347(17)36174-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) antigens, and characterization of tumor-infiltrating mononuclear cells (TIM) were examined immunohistologically in 10 specimens of seminoma. ICAM-1 and MHC antigens were not detected on normal spermatogenic cells. ICAM-1 and MHC class I antigens were variably expressed in 7 and 9 seminomas, respectively, whereas class II antigens were not detected. Although the degree of expression of ICAM-1 and MHC antigens was not correlated with any clinical or histopathological factors, neither of the antigens was detected on an anaplastic seminoma. Various numbers of TIM were detected in all of the seminoma, and comprised mainly T cells bearing the lymphocyte function-associated antigen (LFA)-1. No significant correlation was noticed between the degree of lymphocyte infiltration and ICAM-1 or MHC antigen expression. Although ICAM-1 and MHC class I antigens were expressed in seminoma, possibly facilitating an anti-tumor reaction of host, their expression remained low in several cases, despite marked lymphocyte infiltration within the tumor.
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Affiliation(s)
- Y Tomita
- Department of Urology, Niigata University School of Medicine, Japan
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38
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Schardt C, Heymanns J, Schardt C, Rotsch M, Havemann K. Differential expression of the intercellular adhesion molecule-1 (ICAM-1) in lung cancer cell lines of various histological types. Eur J Cancer 1993; 29A:2250-5. [PMID: 8110495 DOI: 10.1016/0959-8049(93)90217-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Ten small cell lung carcinoma and 12 non-small cell lung carcinoma cell lines of various histological types were studied for constitutive expression of the intercellular adhesion molecule-1 (ICAM-1). ICAM-1 was present in all squamous and large cell carcinoma cell lines whereas two out of five adenocarcinoma and all small cell lung cancer (SCLC) cell lines showed no basal ICAM-1 expression. ICAM-1 expression was upregulated by tumour necrosis factor-alpha (TNF-alpha) in a time- and dose-dependent manner in cell lines with basal ICAM-1 expression. Western blot analysis revealed a molecular size of 85 kDa for ICAM-1 in all but one cell line. The TNF-alpha-induced upregulation of ICAM-1 occurs on the transcriptional level. Adhesion of peripheral blood mononuclear cells to lung tumour cell lines could be inhibited by monoclonal antibodies (MAb) (CD11a;CD18) against the receptor of ICAM-1, the leukocyte function-associated antigen-1 (LFA-1), but not by a MAb (CD54) against ICAM-1 itself.
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Affiliation(s)
- C Schardt
- Department of Hematology/Oncology, Philipps University, Marburg, Germany
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39
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Takahashi T, Ishikura H, Iwai K, Takahashi C, Kato H, Tanabe T, Yoshiki T. Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro. Cancer Immunol Immunother 1993; 36:76-82. [PMID: 8093857 PMCID: PMC11038514 DOI: 10.1007/bf01754405] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/1991] [Accepted: 09/01/1992] [Indexed: 01/28/2023]
Abstract
The permanent pancreas carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on pancreas carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon gamma (IFN gamma) and tumour necrosis factor alpha. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1 beta treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFN gamma in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells, but not of LAK cells, with IFN gamma or other cytokines resulted in a decrease of susceptibility for LAK cell cytotoxicity. The decreased susceptibility inversely correlated with HLA-ABC expression on the PCI cells. The collective evidence indicates that, although LAK cell attachment to pancreas carcinoma cells through the LFA-1/ICAM-1 molecule is augmented by IFN gamma, IFN gamma treatment of pancreas carcinoma cells reduces LAK cell cytotoxicity possibly through an increase in HLA-ABC or a regulation of molecules closely associated to HLA-ABC expression.
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Affiliation(s)
- T Takahashi
- Department of Pathology, Hokkaido University School of Medicine, Sapporo Japan
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40
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Koyama S, Ebihara T, Fukao K. Expression of intercellular adhesion molecule 1 (ICAM-1) during the development of invasion and/or metastasis of gastric carcinoma. J Cancer Res Clin Oncol 1992; 118:609-14. [PMID: 1355484 DOI: 10.1007/bf01211806] [Citation(s) in RCA: 57] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In this study, using two-color flow-cytometric analysis, we examined the expression of histocompatibility locus antigens (HLA) classes I and II, and intercellular adhesion molecule 1 (ICAM-1) in 10 cases of normal gastric mucosa, 13 cases of primary carcinoma on the stomach, 16 cases of metastatic carcinoma from malignant ascites in patients with gastric carcinoma and 14 samples of their cultured carcinoma cells. Compared with normal gastric mucosa, HLA class I were highly expressed in a considerable number of tumor cells in each experimental group. The expression of HLA class II tended to reduce in the order of normal gastric mucosa, primary gastric carcinoma and peritoneal-effusion-associated carcinoma. Altogether, 85.7% of cases of cultured tumor cells showed abrogation and loss of HLA class II. The ICAM-1 molecule was not detected on normal gastric epithelial cells. In few cases, carcinoma cells from large volumes of tumor located in the stomach showed detectable amounts of ICAM-1. On the other hand, all of the metastatic carcinoma cells from peritoneal effusions showed a high level of expression of the ICAM-1 molecule. The expression of ICAM-1 on adenocarcinoma cells was maintained and/or augmented by in vitro cultivation with tumor-infiltrating lymphocytes (TIL). Furthermore, two-color fluorescence-activated cell sorting analysis of TIL revealed that significant correlation was observed between the expression of ICAM-1 and the degree of TIL, composed mainly of CD3+ T cells including CD8+CD11b-, CD8+CD28+, CD8+S6F1+ and CD4+Leu8+, and CD57+CD16- and CD57+CD16+ NK cells, and HLA-DR+LeuM3+ macrophages.
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Affiliation(s)
- S Koyama
- Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan
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41
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Adams DH, Mainolfi E, Burra P, Neuberger JM, Ayres R, Elias E, Rothlein R. Detection of circulating intercellular adhesion molecule-1 in chronic liver diseases. Hepatology 1992; 16:810-4. [PMID: 1354635 DOI: 10.1002/hep.1840160330] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The leucocyte adhesion molecule intercellular adhesion molecule-1 is induced on bile ducts in patients with primary biliary cirrhosis and primary sclerosing cholangitis and may be involved in targeting immune damage to these structures. It has recently been reported that, when activated, in vitro lymphocytes release a soluble form of intercellular adhesion molecule-1 that can also be detected in human serum. Because it is functionally active, this circulating intercellular adhesion molecule-1 might play a role in regulating inflammation by blocking adhesion. We used an enzyme-linked immunosorbent assay to detect circulating intercellular adhesion molecule-1 in the serum of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Levels of circulating intercellular adhesion molecule-1 were markedly elevated in primary biliary cirrhosis and primary sclerosing cholangitis when compared with other chronic liver diseases. Circulating intercellular adhesion molecule-1 is probably derived from activated lymphocytes rather than from bile ducts because biliary epithelial cells from patients with primary biliary cirrhosis did not release circulating intercellular adhesion molecule-1 when stimulated to express the membrane-bound molecule in vitro. These studies are the first to demonstrate circulating intercellular adhesion molecule-1 in chronic inflammatory diseases that are characterized by strong tissue expression of intercellular adhesion molecule-1 and as such suggest a potential immunoregulatory role for circulating adhesion molecules. The very high levels detected in primary biliary cirrhosis and primary sclerosing cholangitis probably reflect lymphocyte activation, which is further evidence of immune pathogeneses for these diseases.
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Affiliation(s)
- D H Adams
- Liver Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom
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42
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Yamaue H, Tanimura H, Tsunoda T, Iwahashi M, Tani M, Tamai M, Noguchi K, Hotta T, Arii K. Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by treatment with the streptococcal preparation OK432. BIOTHERAPY (DORDRECHT, NETHERLANDS) 1992; 5:83-93. [PMID: 1389905 DOI: 10.1007/bf02194788] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by their treatment with OK432. In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.
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MESH Headings
- Antigens, Neoplasm/drug effects
- Antigens, Neoplasm/physiology
- Antigens, Surface/drug effects
- Antigens, Surface/physiology
- Burkitt Lymphoma/metabolism
- Burkitt Lymphoma/pathology
- Burkitt Lymphoma/therapy
- DNA, Neoplasm/biosynthesis
- Humans
- Immunotherapy, Adoptive
- Killer Cells, Lymphokine-Activated/immunology
- Killer Cells, Lymphokine-Activated/metabolism
- Leukemia, Myeloid, Acute/metabolism
- Leukemia, Myeloid, Acute/pathology
- Leukemia, Myeloid, Acute/therapy
- Neoplasms, Experimental/metabolism
- Neoplasms, Experimental/pathology
- Neoplasms, Experimental/therapy
- Phenotype
- Picibanil/pharmacology
- RNA, Neoplasm/biosynthesis
- Sensitivity and Specificity
- Stomach Neoplasms/metabolism
- Stomach Neoplasms/pathology
- Stomach Neoplasms/therapy
- Succinate Dehydrogenase/drug effects
- Succinate Dehydrogenase/metabolism
- Tumor Cells, Cultured/drug effects
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Affiliation(s)
- H Yamaue
- Department of Gastroenterological Surgery, Wakayama Medical College, Japan
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43
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Bouillon M, Fortier MA, Boulianne R, Audette M. Biphasic effect of camp-elevating agents on ICAM-1 expression stimulated by retinoic acid and interferonγ. Int J Cancer 1992; 50:281-8. [PMID: 1370436 DOI: 10.1002/ijc.2910500219] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Incubation of the human glioma cell line HS 683 in the presence of IFN-gamma or retinoic acid strongly stimulates the cell-surface expression of the intercellular adhesion molecule ICAM-1. We have investigated the role of the cAMP-mediated signal transduction pathway in this process and report that pharmacological agents which increased the intracellular levels of cAMP exhibited a biphasic action on ICAM-1 expression in human glioma cell line HS 683. Treatment for 1 hr with 25 microM forskolin or 1 mM isobutylmethylxanthine, or for 12 hr with 100 ng/ml pertussis toxin or 50 micrograms/ml cholera toxin transiently stimulated ICAM-1 expression with a maximal level of expression 8 hr post treatment, after which time ICAM-1 expression returned to the basal level. On the other hand, such pretreatments inhibited the inducing effects of either retinoic acid or IFN-gamma. Indeed, 24 hr after treatment with cAMP-elevating agents, both the retinoic-acid- and the IFN-gamma-induced ICAM-1 expression were inhibited by 60 to 80%, with a maximal 90 to 100% inhibition 72 hr post treatment. This inhibition of the cell-surface expression of ICAM-1 was confirmed at the mRNA level. The intracytoplasmic levels of cAMP were also quantified following treatments with forskolin, retinoic acid or IFN-gamma. In response to forskolin, cAMP levels increased 30-fold within 5 min, whereas a 10-fold increase occurred 60 min following treatment with 10 microM retinoic acid. Interferon gamma, in contrast, did not induce cAMP accumulation. These results were also correlated with an in vitro activation of adenylyl cyclase activity by retinoic acid and inhibition of this activity by IFN-gamma, in a dose-dependent and a GTP-dependent manner. Our results suggest that the suppression of IFN-gamma-induced ICAM-1 expression, obtained upon pre-treatment with cAMP-elevating agents, is due to direct antagonism with IFN-gamma action on adenylyl cyclase. However, the inhibition of retinoic-acid-induced ICAM-1 expression cannot be explained by the same mechanisms. The timing of adenylyl cyclase stimulation and cAMP accumulation, as well as the levels of cAMP accumulation, are probably involved in this inhibition. Our results also emphasize the fact that the induction of ICAM-1 expression is a multi-step process implicating different transductional signals among which cAMP might be involved as a second messenger.
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Affiliation(s)
- M Bouillon
- Molecular Endocrinology Unit, CHUL Research Center, Laval University, Ste-Foy, Quebec, Canada
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44
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Bouillon M, Tessier P, Boulianne R, Destrempe R, Audette M. Regulation by retinoic acid of ICAM-1 expression on human tumor cell lines. BIOCHIMICA ET BIOPHYSICA ACTA 1991; 1097:95-102. [PMID: 1680399 DOI: 10.1016/0925-4439(91)90091-m] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
In a group of four human tumor cell lines comprising one melanoma, one glioma, one teratocarcinoma and one neuroblastoma, the expression of the intercellular adhesion molecule-1 (ICAM-1) was found to be significantly increased following treatment with 10 microM of all-trans retinoic acid. In the melanoma and glioma cell lines HS 294T and HS 683, greater than 90% of the cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) CL203.4 in the absence of treatment. Retinoic acid increased the cell surface expression of the molecule by 2-fold. In the teratocarcinoma and neuroblastoma cell lines, TERA-2 and SK-N-SH, the constitutive expression of ICAM-1 was weak, the percentage of cells stained above the background being less than 25%. Retinoic acid induced ICAM-1 expression in greater than 80% of the cells and increased the levels of expression by 2.5 to 3-fold. Immunoprecipitation studies in biosynthetically labeled cells as well as RNase protection analysis confirmed that retinoic acid treatment increased the amount of ICAM-1 at both the protein and mRNA level. The induction or stimulation occurred within 24 h, was maximal after 4 days and reversible.
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Affiliation(s)
- M Bouillon
- CHUL Research Center, Faculty of Medicine, Laval University, Quebec City, Canada
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45
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Favrot MC, Combaret V, Goillot E, Tabone E, Bouffet E, Dolbeau D, Bouvier R, Coze C, Michon J, Philip T. Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens. Int J Cancer 1991; 48:502-10. [PMID: 1710608 DOI: 10.1002/ijc.2910480405] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
LFA-3, ICAM-1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA-3 on 20 and ICAM-1 on 10. HLA.ABC and LFA-3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA-3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM-1 was restricted to 5 of the 10 low-grade stage-1 or stage-2 specimens, 1 stage-3 specimen, and the primary tumors of 2 patients with stage-4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA-3 expressed on both mycN-negative and -positive specimens, whereas ICAM-1 was restricted to MYCN-negative specimens. LFA-3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM-1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM-1-negative, suggesting ICAM-1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN-gamma.
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46
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Mölgg M, Schwaeble W, Johnson JP, Dierich MP. Generation of recombinant, carbohydrate-free intercellular adhesion molecule-1 (ICAM-1) and ICAM-1 fragments in Escherichia coli and mapping of epitopes recognized by anti-ICAM-1 monoclonal antibodies. Immunol Lett 1991; 28:237-43. [PMID: 1715847 DOI: 10.1016/0165-2478(91)90010-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Intercellular adhesion molecule-1 (ICAM-1) has been shown to interact with the integrin leukocyte function associated antigen-1 (LFA-1) in a variety of cell-cell adhesion phenomena. Furthermore, it serves as a receptor for the majority of the Rhinoviruses and for Plasmodium falciparum-infected human erythrocytes. We generated recombinant, carbohydrate-free ICAM-1 and several ICAM-1 fragments by expression in Escherichia coli using the fusion protein expression system pUEX1-3. In Western blot and dot blot analyses we tested mAbs (7F7, 8B9, P3.58-BA3, -BA11, -BA14, -BA19, -BA21, -BA23, -BA24, -BA26, CL203.4 and 84H10) and a polyclonal antiserum directed against native ICAM-1 for their reactivity with these constructs. We were able to localize the binding site for the mAbs P3.58-BA3, -BA11, -BA14, -BA19, -BA21, -BA23, -BA24 and -BA26 at domain 5, whereas the mAbs 7F7, 8B9, CL203.4 and 84H10 did not recognize the recombinant, carbohydrate-free ICAM-1. Our findings suggest the presence of an immunodominant epitope on domain 5 of ICAM-1.
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Affiliation(s)
- M Mölgg
- Institut für Hygiene, University of Innsbruck, Austria
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47
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Vogetseder W, Dierich MP. Intercellular adhesion molecule-1 (ICAM-1, CD 54) is associated with actin-filaments. Immunobiology 1991; 182:143-51. [PMID: 1679412 DOI: 10.1016/s0171-2985(11)80198-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Intercellular adhesion molecule 1 (ICAM-1, CD 54) is a membrane associated glycoprotein involved in cell-cell interactions of the immune system. Detergent extraction of cultured human fibroblasts--stimulated with Interferon-gamma (IFN-gamma) for ICAM-1-expression--under conditions that stabilize actin in the filamentous (actin-F) form (NaF-buffer, phalloidine) resulted in greater retention of ICAM-1 in the detergent insoluble phase, containing the cytoskeletal matrix, compared to actin-F-destabilizing conditions (KCl-buffer). We further examined the in vitro ICAM-1 association with actin using immunoaffinity purified ICAM-1, prepared from either normal human tonsils or a spleen derived from a patient with Non-Hodgkin's lymphoma. ICAM-1 from both sources demonstrated binding to actin coated polystyrene surfaces. Our findings suggest that ICAM-1 interacts with actin-F and may use similar mechanisms described with other adhesion molecules for membrane-cytosol communication.
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Affiliation(s)
- W Vogetseder
- Institute for Hygiene, University of Innsbruck, Austria
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Tomita Y, Nishiyama T, Watanabe H, Fujiwara M, Sato S. Expression of intercellular adhesion molecule-1 (ICAM-1) on renal-cell cancer: possible significance in host immune responses. Int J Cancer 1990; 46:1001-6. [PMID: 1979067 DOI: 10.1002/ijc.2910460609] [Citation(s) in RCA: 66] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
In this study we examined the expression of intercellular adhesion molecule-1 (ICAM-1) in 28 cases of renal-cell cancer (RCC). We also examined ICAM-1 expression on RCC cell lines in response to cytokines. Immunohistochemistry revealed frequent expression (23 positive cases among the 28 RCCs) of ICAM-1 in RCC. The molecule was not detected on renal tubular cells as far as could be determined. Furthermore, the number of ICAM-1-positive cells in RCC was significantly correlated with the degree of mononuclear cell infiltration, involving mainly T lymphocytes and a smaller number of macrophages bearing the LFA-1 molecule. Expression of ICAM-1 on RCC cell lines was augmented by in vitro treatment with interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1)beta. These results suggest that the expression of ICAM-1 on RCC might be modified by cytokines produced by tumor-infiltrating mononuclear cells, and that ICAM-1 expression on RCC might augment the host immune reaction.
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Affiliation(s)
- Y Tomita
- Department of Immunology, Niigata University, School of Medicine, Japan
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Guarini L, Temponi M, Bruce JN, Bollon AP, Duigou GJ, Moulton TA, Ferrone S, Fisher PB. Expression and modulation by cytokines of the intercellular adhesion molecule-1 (ICAM-1) in human central nervous system tumor cell cultures. Int J Cancer 1990; 46:1041-7. [PMID: 1979069 DOI: 10.1002/ijc.2910460616] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The intercellular adhesion molecule (ICAM-1) has been shown to be important in interactions involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In the present study, we have determined by fluorescence-activated cell sorter (FACS) analysis and the anti-ICAM-1 monoclonal antibody (MAb) CL203.4 the base-line expression of ICAM-1 and its modulation by recombinant IFN-beta, IFN-gamma and TNF-alpha in early passage (less than 15) human central nervous system (CNS) tumor-derived cell cultures. These cultures were established from various malignancies, including glioblastoma multiforme (GBM), astrocytoma (AST), ganglioglioma, medulloblastoma, meningioma and a pineal tumor. ICAM-1 expression was highest in the GBM- and AST-derived cell cultures and was lowest in the ganglioglioma and normal pineal cell cultures. Variable ICAM-1 expression was found, however, in tumors of the same histological group. In several cell cultures the variable expression observed by FACS was substantiated by the intensity of the molecular species immunoprecipitated by the anti-ICAM-1 MAb CL203.4 from these cells. All the cell cultures displayed variable but consistent increases in ICAM-1 expression following treatment with IFN-gamma or TNF-alpha. In general, the degree of increase in ICAM-1 expression was greatest in cultures exposed to TNF-alpha. Upregulation of ICAM-1 expression in an established glioblastoma multiforme cell line was of greater magnitude and more rapid following TNF-alpha treatment (within 2 to 3 hr) than exposure to IFN-gamma (by 24 hr). In several cultures, IFN-beta also increased ICAM-1 expression and enhanced the increase induced by TNF-alpha. The results of the present study indicate that variable expression of ICAM-1 is a common property of early passage cultures of CNS tumors and recombinant interferons and TNF-alpha can differentially upregulate ICAM-1 expression in these CNS tumor cell cultures.
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Affiliation(s)
- L Guarini
- Division of Pediatric Hematology/Oncology, Columbia University, College of Physicians and Surgeons, New York, NY 10032
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Stade BG, Messer G, Riethmüller G, Johnson JP. Structural characteristics of the 5' region of the human ICAM-1 gene. Immunobiology 1990; 182:79-87. [PMID: 1983003 DOI: 10.1016/s0171-2985(11)80585-1] [Citation(s) in RCA: 63] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The ICAM-1 glycoprotein, one of the major cellular adhesion molecules, exhibits a diverse and highly regulated tissue distribution. To better understand the regulatory mechanisms underlying its particular expression pattern, we have cloned the ICAM-1 gene from human leukocyte libraries. By hybridization with various DNA probes derived from different regions of the ICAM-1 cDNA, several clones were identified and isolated. Clone HWB 3R1, containing a 15kb DNA insert, was selected for further characterization. The HWB 3R1 clone hybridized with probes corresponding to the 3' as well as the 5' region of the ICAM-1 cDNA and gave rise to ICAM-1 expression after transfection into the ICAM-1 deficient MJP17 melanoma cell line. The identity of the expressed ICAM-1 was verified by reaction with five different monoclonal antibodies specific for ICAM-1. Sequence analysis of about 1.2kb of DNA around the ATG start codon revealed putative binding sites for various transcription factors situated in the 5' untranslated region as well as within the first intron. These include SP-1, AP-1 and NF-kB binding sites as well as interferon and retinoic acid responsive elements.
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Affiliation(s)
- B G Stade
- Institute of Immunology, Munich, Federal Republic of Germany
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