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Dastych M, Hubatka F, Turanek-Knotigova P, Masek J, Kroupa R, Raška M, Turanek J, Prochazka L. Overexpression of CD44v8-10 in Colon Polyps-A Possible Key to Early Diagnosis. Pathol Oncol Res 2021; 27:614281. [PMID: 34257584 PMCID: PMC8262190 DOI: 10.3389/pore.2021.614281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 02/26/2021] [Indexed: 01/10/2023]
Abstract
Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon. Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses. Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner. Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique. Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma.
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Affiliation(s)
- Milan Dastych
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine Masaryk University Brno, Brno, Czech Republic
| | - Frantisek Hubatka
- Department of Pharmacology and Toxicology, Veterinary Research Institute, Brno, Czech Republic.,C2P NEXARS, Campus Science Park, Brno, Czech Republic
| | - Pavlina Turanek-Knotigova
- Department of Pharmacology and Toxicology, Veterinary Research Institute, Brno, Czech Republic.,C2P NEXARS, Campus Science Park, Brno, Czech Republic
| | - Josef Masek
- Department of Pharmacology and Toxicology, Veterinary Research Institute, Brno, Czech Republic
| | - Radek Kroupa
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine Masaryk University Brno, Brno, Czech Republic
| | - Milan Raška
- Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
| | - Jaroslav Turanek
- Department of Pharmacology and Toxicology, Veterinary Research Institute, Brno, Czech Republic.,C2P NEXARS, Campus Science Park, Brno, Czech Republic.,Faculty of Medicine in Hradec Kralove, Institute of Hygiene and Preventive Medicine, Charles University, Hradec Kralove, Czech Republic.,Institute of Physics of the Czech Academy of Sciences, Prague 8, Czech Republic
| | - Lubomir Prochazka
- Department of Pharmacology and Toxicology, Veterinary Research Institute, Brno, Czech Republic
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Hartmans E, Orian-Rousseau V, Matzke-Ogi A, Karrenbeld A, de Groot DJA, de Jong S, van Dam GM, Fehrmann RS, Nagengast WB. Functional Genomic mRNA Profiling of Colorectal Adenomas: Identification and in vivo Validation of CD44 and Splice Variant CD44v6 as Molecular Imaging Targets. Am J Cancer Res 2017; 7:482-492. [PMID: 28255344 PMCID: PMC5327362 DOI: 10.7150/thno.16816] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 11/07/2016] [Indexed: 12/17/2022] Open
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. High adenoma miss rates, especially seen in high-risk patients, demand for better endoscopic detection. By fluorescently 'highlighting' specific molecular characteristics, endoscopic molecular imaging has great potential to fulfill this need. To implement this technique effectively, target proteins that distinguish adenomas from normal tissue must be identified. In this study we applied in silico Functional Genomic mRNA (FGmRNA) profiling, which is a recently developed method that results in an enhanced view on the downstream effects of genomic alterations occurring in adenomas on gene expression levels. FGmRNA profiles of sporadic adenomas were compared to normal colon tissue to identify overexpressed genes. We validated the protein expression of the top identified genes, AXIN2, CEMIP, CD44 and JUN, in sporadic adenoma patient samples via immunohistochemistry (IHC). CD44 was identified as the most attractive target protein for imaging purposes and we proved its relevance in high-risk patients by demonstrating CD44 protein overexpression in Lynch lesions. Subsequently, we show that the epithelial splice variant CD44V6 is highly overexpressed in our patient samples and we demonstrated the feasibility of visualizing adenomas in ApcMin/+ mice in vivo by using a fluorescently labeled CD44v6 targeting peptide. In conclusion, via in silico functional genomics and ex vivo protein validation, this study identified CD44 as an attractive molecular target for both sporadic and high-risk Lynch adenomas, and demonstrates the in vivo applicability of a small peptide drug directed against splice variant CD44v6 for adenoma imaging.
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Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis. Int J Cell Biol 2015; 2015:834893. [PMID: 26448760 PMCID: PMC4581578 DOI: 10.1155/2015/834893] [Citation(s) in RCA: 123] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Accepted: 04/01/2015] [Indexed: 02/06/2023] Open
Abstract
A wound is a type of injury that damages living tissues. In this review, we will be referring mainly to healing responses in the organs including skin and the lungs. Fibrosis is a process of dysregulated extracellular matrix (ECM) production that leads to a dense and functionally abnormal connective tissue compartment (dermis). In tissues such as the skin, the repair of the dermis after wounding requires not only the fibroblasts that produce the ECM molecules, but also the overlying epithelial layer (keratinocytes), the endothelial cells, and smooth muscle cells of the blood vessel and white blood cells such as neutrophils and macrophages, which together orchestrate the cytokine-mediated signaling and paracrine interactions that are required to regulate the proper extent and timing of the repair process. This review will focus on the importance of extracellular molecules in the microenvironment, primarily the proteoglycans and glycosaminoglycan hyaluronan, and their roles in wound healing. First, we will briefly summarize the physiological, cellular, and biochemical elements of wound healing, including the importance of cytokine cross-talk between cell types. Second, we will discuss the role of proteoglycans and hyaluronan in regulating these processes. Finally, approaches that utilize these concepts as potential therapies for fibrosis are discussed.
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Ghatak S, Bogatkevich GS, Atnelishvili I, Akter T, Feghali-Bostwick C, Hoffman S, Fresco VM, Fuchs JC, Visconti RP, Markwald RR, Padhye SB, Silver RM, Hascall VC, Misra S. Overexpression of c-Met and CD44v6 receptors contributes to autocrine TGF-β1 signaling in interstitial lung disease. J Biol Chem 2013; 289:7856-72. [PMID: 24324260 DOI: 10.1074/jbc.m113.505065] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The hepatocyte growth factor (HGF) and the HGF receptor Met pathway are important in the pathogenesis of interstitial lung disease (ILD). Alternatively spliced isoforms of CD44 containing variable exon 6 (CD44v6) and its ligand hyaluronan (HA) alter cellular function in response to interaction between CD44v6 and HGF. TGF-β1 is the crucial cytokine that induces fibrotic action in ILD fibroblasts (ILDFbs). We have identified an autocrine TGF-β1 signaling that up-regulates both Met and CD44v6 mRNA and protein expression. Western blot analysis, flow cytometry, and immunostaining revealed that CD44v6 and Met colocalize in fibroblasts and in tissue sections from ILD patients and in lungs of bleomycin-treated mice. Interestingly, cell proliferation induced by TGF-β1 is mediated through Met and CD44v6. Further, cell proliferation mediated by TGF-β1/CD44v6 is ERK-dependent. In contrast, action of Met on ILDFb proliferation does not require ERK but does require p38(MAPK). ILDFbs were sorted into CD44v6(+)/Met(+) and CD44v6(-)/Met(+) subpopulations. HGF inhibited TGF-β1-stimulated collagen-1 and α-smooth muscle cell actin expression in both of these subpopulations by interfering with TGF-β1 signaling. HGF alone markedly stimulated CD44v6 expression, which in turn regulated collagen-1 synthesis. Our data with primary lung fibroblast cultures with respect to collagen-1, CD44v6, and Met expressions were supported by immunostaining of lung sections from bleomycin-treated mice and from ILD patients. These results define the relationships between CD44v6, Met, and autocrine TGF-β1 signaling and the potential modulating influence of HGF on TGF-β1-induced CD44v6-dependent fibroblast function in ILD fibrosis.
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Affiliation(s)
- Shibnath Ghatak
- From the Department of Regenerative Medicine and Cell Biology and
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Misra S, Ghatak S, Patil N, Dandawate P, Ambike V, Adsule S, Unni D, Venkateswara Swamy K, Padhye S. Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells. Bioorg Med Chem 2013; 21:2551-9. [PMID: 23517721 DOI: 10.1016/j.bmc.2013.02.033] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Revised: 02/12/2013] [Accepted: 02/21/2013] [Indexed: 12/28/2022]
Abstract
Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme have been found to play a role in promoting growth in colon cancer cell lines. The di-tert-butyl phenol class of compounds has been found to inhibit both COX-2 and 5-LOX enzymes with proven effectiveness in arresting tumor growth. In the present study, the structural analogs of 2,6 di-tert-butyl-p-benzoquinone (BQ) appended with hydrazide side chain were found to inhibit COX-2 and 5-LOX enzymes at micromolar concentrations. Molecular docking of the compounds into COX-2 and 5-LOX protein cavities indicated strong binding interactions supporting the observed cytototoxicities. The signaling interaction between endogenous hyaluronan and CD44 has been shown to regulate COX-2 activities through ErbB2 receptor tyrosine kinase (RTK) activation. In the present studies it has been observed for the first time, that three of our COX/5-LOX dual inhibitors inhibit proliferation upon hydrazide substitution and prevent the activity of pro-angiogenic factors in HCA-7, HT-29, Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressed in colon cancer cells, through inhibition of the hyaluronan/CD44v6 cell survival pathway. Since there is a substantial enhancement in the antiproliferative activities of these compounds upon hydrazide substitution, the present work opens up new opportunities for evolving novel active compounds of BQ series for inhibiting colon cancer.
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Affiliation(s)
- Suniti Misra
- Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
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Saito S, Okabe H, Watanabe M, Ishimoto T, Iwatsuki M, Baba Y, Tanaka Y, Kurashige J, Miyamoto Y, Baba H. CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer. Oncol Rep 2013; 29:1570-8. [PMID: 23404221 DOI: 10.3892/or.2013.2273] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Accepted: 12/25/2012] [Indexed: 12/14/2022] Open
Abstract
CD44 standard isoform (CD44s) is a cancer stem cell marker in many tumors, and is one of the CD44 isoforms.CD44v6 has been reported to correlate with tumor progression and poor prognosis in colorectal cancer. However, the relevance of CD44s and CD44v6 to epithelial-mesenchymal transition (EMT) remains unclear. Immunohistochemistry was performed to investigate the clinical importance of CD44s and CD44v6 and their relevance to EMT in 113 patients with stage II/III colorectal cancer treated by curative resection. The relevance of CD44v6 knockdown to the phenotype of colon cancer cells was examined using small interfering RNA (siRNA) specific for CD44v6 in vitro. CD44v6 expression showed a significant inverse correlation with E-cadherin expression (P=0.0007) and a positive correlation with vimentin expression (P=0.0096). A multivariate analysis showed that high CD44v6 expression was an independent poor prognostic factor for disease-free survival (P=0.01, HR=3.05) and overall survival (P=0.025, HR=3.16). The clinical significance and the relevance of CD44s expression to EMT markers was noted to a lesser extent compared to CD44v6 expression. The knockdown of CD44v6 decreased vimentin expression, cell invasion and HGF-induced cell migration, but conferred only a slight effect on E-cadherin expression in colon cancer cells (HCT116 and LoVo). CD44v6 is related to poor outcome of patients with colorectal cancer via upregulation of the mesenchymal phenotype.
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Affiliation(s)
- Seiya Saito
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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Zlobec I, Günthert U, Tornillo L, Iezzi G, Baumhoer D, Terracciano L, Lugli A. Systematic assessment of the prognostic impact of membranous CD44v6 protein expression in colorectal cancer. Histopathology 2010; 55:564-75. [PMID: 19912362 DOI: 10.1111/j.1365-2559.2009.03421.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AIMS To assess systematically the membranous expression of CD44v6 in colorectal cancer by immunohistochemistry to determine its prognostic impact, the differential expression between primary and metastatic tumours and expression differences between the tumour centre and invasive front. METHODS AND RESULTS Immunohistochemistry was performed for CD44v6 on two tissue microarrays. The first included 1279 colorectal tumours with full clinicopathological data. The second consisted of 50 matched primary and metastatic tumours sampled from the tumour centre and the invasive margin. A scoring system was tested by multiple observers. Receiver-operating characteristic curve analysis was used for cut-off point determination. Loss of membranous CD44v6 was associated with pT stage (P = 0.016; sensitivity 85.8%, specificity 20.1%), lymph node metastasis (P = 0.015; sensitivity 52.8%, specificity 55%), an infiltrating tumour margin (P < 0.001; sensitivity 71.4%, specificity 40%) and adverse prognosis (P = 0.011; hazard ratio 0.79, 95% confidence interval 0.7, 0.9), but was not an independent prognostic factor on multivariable analysis. Loss of expression occurred at the invasive front in both primary and metastatic lesions (P < 0.001). CONCLUSIONS This study outlines an approach to help standardize the immunohistochemical evaluation of CD44v6 and similar markers in colorectal cancer and highlights a significant role for loss of membranous CD44v6 expression in colorectal cancer progression and prognosis.
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Affiliation(s)
- Inti Zlobec
- Institute of Pathology,University Hospital of Basel, Basel, Switzerland.
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Vizoso FJ, Fernández JC, Corte MD, Bongera M, Gava R, Allende MT, García-Muñiz JL, García-Morán M. Expression and clinical significance of CD44V5 and CD44V6 in resectable colorectal cancer. J Cancer Res Clin Oncol 2004; 130:679-86. [PMID: 15300427 DOI: 10.1007/s00432-004-0596-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2003] [Accepted: 05/26/2004] [Indexed: 01/17/2023]
Abstract
PURPOSE This study was conducted to evaluate the prognostic significance of CD44v5 and CD44v6 in resectable colorectal cancer. MATERIALS AND METHODS Membranous CD44v5 and CD44v6 levels were measured by an immunoenzymatic assay in tumors and surrounding mucosal samples obtained from 105 patients with resectable colorectal carcinomas. RESULTS There were no significant differences of CD44v5 levels between tumors [median: 3.2 (range: 0.9-83.5) ng/mg protein) and surrounding mucosal samples (3 (3-146.2) ng/mg protein]. However, tumor samples showed significantly higher CD44v6 levels [19.5 (2.2-562.9) ng/mg protein] than mucosal samples [5 (5-230) ng/mg protein] (P=0.0001). Patients with higher CD44v5 or CD44v6 content in tumor samples had a considerably shorter relapse-free survival (P<0.05, for both). Patients with a higher CD44v6 content also had a shorter relapse-free and overall survival in the multivariate analysis (P<0.05). CONCLUSION The results of this study suggest a role of CD44v5 and CD44v6 in colorectal cancer progression. Membranous CD44v levels in primary tumors, measured by immunoenzymatic assay, may contribute to a more precise prognostic estimation in patients with resectable colorectal cancer.
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Affiliation(s)
- Francisco J Vizoso
- Servicio de Cirugía General, Hospital de Jove, Avda. Eduardo Castro s/n, 33920, Gijón, Asturias, Spain,
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Yue SQ, Yang YL, Dou KF, Li KZ. Expression of PCNA and CD44mRNA in colorectal cancer with venous invasion and its relationship to liver metastasis. World J Gastroenterol 2003; 9:2863-5. [PMID: 14669354 PMCID: PMC4612073 DOI: 10.3748/wjg.v9.i12.2863] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the expression of proliferating cell nuclear antigen (PCNA) and CD44mRNA in colorectal cancer with venous invasion and its relationship with liver metastasis.
METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of PCNA and CD44mRNA in 31 cases of colorectal cancer with venous invasion.
RESULTS: Positive expression rates of PCNA and CD44mRNA in colorectal cancer were higher than those without liver metastasis (P < 0.05 and P < 0.01). In case of colorectal cancer with liver metastasis, strongly positive rates of PCNA and CD44mRNA were 94.1% and 70.6%, respectively, significantly higher than those without liver metastasis. There was a positive relationship between the expressions of PCNA and CD44mRNA (r = 0.67, P < 0.05).
CONCLUSION: Detection of PCNA and CD44mRNA expression in colorectal cancer may be useful for evaluating liver metastasis of cancer cells.
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Affiliation(s)
- Shu-Qiang Yue
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
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Carr NJ, Emory TS, Sobin LH. Epithelial neoplasms of the appendix and colorectum: an analysis of cell proliferation, apoptosis, and expression of p53, CD44, bcl-2. Arch Pathol Lab Med 2002; 126:837-41. [PMID: 12088454 DOI: 10.5858/2002-126-0837-enotaa] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT Carcinomas of the appendix are usually well-differentiated mucinous adenocarcinomas that tend to produce pseudomyxoma peritonei and do not show metastatic spread until late in the disease process. In contrast, adenocarcinomas of the colon and rectum rarely result in pseudomyxoma peritonei and frequently metastasize, even if mucinous and well differentiated. These differences in behavior may be reflected by differences at the molecular level. OBJECTIVES To examine adenocarcinomas and their precursor lesions (adenomas) of the appendix and colorectum and to determine whether differences exist in the numbers of proliferating and apoptotic cells or in expression of p53, bcl-2, and the standard form of CD44 (CD44s). DESIGN Retrospective analysis of surgical specimens. SETTING Multicenter study. PATIENTS Individuals treated surgically for tumors of the appendix or colorectum. INTERVENTIONS Sections were cut from formalin-fixed surgical specimens and immunohistochemical tests were performed for Ki-67 (as a marker of proliferating cells), M30 (as a marker of apoptotic cells), p53, CD44s, and bcl-2. MAIN OUTCOME MEASURES Expression of Ki-67, M30, p53, CD44s, and bcl-2 in tumor cells. RESULTS The appendiceal adenomas showed significantly lower Ki-67 counts, p53 expression, and bcl-2 expression. When compared with adenocarcinomas of the colorectum in general (mucinous and nonmucinous), the appendiceal adenocarcinomas showed significantly lower Ki-67 counts, M30 counts, and CD44s expression. However, when the analysis was confined to well-differentiated mucinous adenocarcinomas, only the M30 count was significantly different. CONCLUSIONS The lower proliferative and apoptotic activity of appendiceal carcinomas and the lower CD44s expression are in keeping with their more indolent behavior compared with adenocarcinomas of the colorectum. However, when only the subset of well-differentiated mucinous adenocarcinomas was compared, only the apoptotic activity was different, suggesting that the other differences were related to the morphologic structure of the lesions.
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Affiliation(s)
- Norman J Carr
- Department of Cellular Pathology, Southampton University Hospitals National Health Service Trust, Southampton, Hampshire, England.
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Ni HM, Leong AFPK, Cheong D, Hooi SC. Expression of CD44 variants in colorectal carcinoma quantified by real-time reverse transcriptase-polymerase chain reaction. THE JOURNAL OF LABORATORY AND CLINICAL MEDICINE 2002; 139:59-65. [PMID: 11873246 DOI: 10.1067/mlc.2002.120425] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
CD44 is a family of transmembrane glycoproteins that has been linked to carcinogenesis and metastasis. It serves as a major receptor for hyaluronate. The v3 isoform binds to growth factors through heparan sulfate side chains and targets these factors to their high-affinity signal transducing receptors. The purpose of this study was to analyze the expression of CD44 v3 and v4 in human colorectal carcinoma with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Our results show that 19 of 56 cases (33.9%) showed a greater than 2-fold increase in CD44 v3 expression in tumors as compared with matched normal mucosa, while 15 of 44 cases (34.1%) showed a greater than 2-fold increase in CD44 v4 expression. There was a marked variation in fold-differences of CD44 gene expression between tumor and normal samples (T/N ratios) among the tumors. This prompted us to correlate the T/N ratios of the tumors with clinicopathologic characteristics. Interestingly, overexpression of CD44 v3 mRNA was associated with the presence of vascular invasion (P <.05). Similarly, overexpression of CD44 v4 was significantly correlated to increased depth of invasion (P <.05). Results from the present study suggest that overexpression of CD44 v3 and v4 mRNA levels may be useful clinical markers for colorectal carcinoma invasiveness.
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Affiliation(s)
- Hong-Min Ni
- Department of Physiology, Faculty of Medicine, National University of Singapore, Singapore
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Imam H, Eriksson B, Oberg K. Expression of CD44 variant isoforms and association to the benign form of endocrine pancreatic tumours. Ann Oncol 2000; 11:295-300. [PMID: 10811495 DOI: 10.1023/a:1008333812548] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The expression of CD44 and its isoforms have been shown in many neoplastic tissues to serve as prognostic indicators, therefore, the feasibility of using these as prognostic markers in endocrine pancreatic tumour patients was examined. PATIENTS AND METHODS Immunohistochemistry (IHC) was performed on 26 tumour samples (5 gastrinomas, 3 glucagonomas, 10 non-functioning tumours, 6 insulinomas, 2 mixed insulinoma and glucagonomas) with monoclonal antibodies against CD44s (standard form) and variant isoforms (v4, v5, v6, v7, v7-8, v9, v10). Staining was correlated to the tumour proliferation, malignancy, metastasis and patients survival. RESULTS There was variable expression of CD44s. All tumours showed complex expression of many isoforms. CD44v6 and CD44v9 were down regulated in malignant tumours. There was statistical significance of CD44v6 expression in benign tumours (P < 0.05) compared to malignant tumours and near significance in CD44v9 expression (P = 0.0574). Survival of the patients with CD44v6 positive staining was higher than those who were negative (P = 0.0822). Moreover, the expression was well correlated to the patients without any distant metastases (CD44v6, p < 0.001; CD44v9, P < 0.01). Tumour proliferation (Ki67 index) correlated directly to the malignancy (P < 0.05) and there was inverse correlation between Ki67 index and CD44v6 (P < 0.05) as well as v9 (P < 0.05). CONCLUSIONS Endocrine pancreatic tumours express CD44s and isoforms differentially. Expression of the two isoforms of CD44, namely v6 and v9 seem to be related more to benign form of the tumour and could serve as a predictor of good prognosis.
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Affiliation(s)
- H Imam
- Department of Internal medicine, University Hospital, Uppsala, Sweden
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