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For: Gires O, Stoecklein NH. Dynamic EpCAM expression on circulating and disseminating tumor cells: causes and consequences. Cell Mol Life Sci 2014;71:4393-402. [PMID: 25103341 PMCID: PMC11113679 DOI: 10.1007/s00018-014-1693-1] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 07/22/2014] [Accepted: 07/24/2014] [Indexed: 12/19/2022]

For:	Gires O, Stoecklein NH. Dynamic EpCAM expression on circulating and disseminating tumor cells: causes and consequences. Cell Mol Life Sci 2014;71:4393-402. [PMID: 25103341 PMCID: PMC11113679 DOI: 10.1007/s00018-014-1693-1] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 07/22/2014] [Accepted: 07/24/2014] [Indexed: 12/19/2022]

Number

Cited by Other Article(s)

Fabisiewicz A, Szostakowska-Rodzos M, Grzybowska EA. Improving the Prognostic and Predictive Value of Circulating Tumor Cell Enumeration: Is Longitudinal Monitoring the Answer? Int J Mol Sci 2024;25:10612. [PMID: 39408942 PMCID: PMC11476589 DOI: 10.3390/ijms251910612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 09/27/2024] [Accepted: 09/30/2024] [Indexed: 10/20/2024] Open

Huang L, Huang H, Zhang Z, Li G. Three-Dimensional DNA Hydrogel Mediated Dual-Mode Sensing Method for Quantification of Epithelial Cell Adhesion Molecule in Biological Fluid Samples. Anal Chem 2024. [PMID: 39007488 DOI: 10.1021/acs.analchem.4c01006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/16/2024]

Abstract

Monitoring changes in the expression of marker proteins in biological fluids is essential for biomarker-based disease diagnosis. Epithelial cell adhesion molecule (EpCAM) has been identified as a broad-spectrum biomarker for various chronic diseases and as a therapeutic target. However, the development of simple and reliable methods for quantifying EpCAM changes in biological fluids faces challenges due to the variability of its expression across different diseases, the presence of soluble forms, and matrix effects. In this paper, a surface-enhanced Raman scattering (SERS)-fluorescence (FL) dual-mode sensing method was established for quantification of trace EpCAM in biological fluids based on bimetallic Au@Ag nanoparticles and nitrogen-doped quantum dots encapsulated DNA hydrogel hybrid with graphene oxide (Au@Ag-NQDs/GO). The DNA hydrogel was constructed based on three-dimensional (3D) structure DNA-mediated strategy using an aptamer DNA (AptDNA) linker. The interaction of the AptDNA with EpCAM triggered the disassembly of the DNA hydrogel. Consequently, the release of Au@Ag nanoparticles induced an "on-off" switch in the SERS signal while the weakened FL quenching effect in Au@Ag-NQDs/GO system achieved "off-on" switch of FL signal, enabling the simultaneous SERS-FL quantification of EpCAM. The established dual-mode method exhibited outstanding sensitivity and stability in quantifying EpCAM in the range of 0.5-60.0 pg/mL, with the limits of detection (LODs) of SERS and FL as 0.17 and 0.35 pg/mL, respectively. When applied for real sample analysis, the method showed satisfactory specificity and recoveries in cancer cells lysate, serum, and urine samples with RSDs of 2.8-6.3%, 4.0-6.3%, and 2.8-5.7%, respectively. The developed SERS-FL sensing method offered a sensitive, reliable, and practical quantification strategy for trace EpCAM in diverse biological fluid samples, which would benefit the early diagnosis of disease and further health management.

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Zhang Z, Chen W, Sun M, Aalders T, Verhaegh GW, Kouwer PHJ. TempEasy 3D Hydrogel Coculture System Provides Mechanistic Insights into Prostate Cancer Bone Metastasis. ACS APPLIED MATERIALS & INTERFACES 2024;16:25773-25787. [PMID: 38739686 PMCID: PMC11129143 DOI: 10.1021/acsami.4c03453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 05/16/2024]

Stoecklein NH, Oles J, Franken A, Neubauer H, Terstappen LWMM, Neves RPL. Clinical application of circulating tumor cells. MED GENET-BERLIN 2023;35:237-250. [PMID: 38835741 PMCID: PMC11110132 DOI: 10.1515/medgen-2023-2056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2024]

Temilola DO, Adeola HA, Grobbelaar J, Chetty M. Liquid Biopsy in Head and Neck Cancer: Its Present State and Future Role in Africa. Cells 2023;12:2663. [PMID: 37998398 PMCID: PMC10670726 DOI: 10.3390/cells12222663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/12/2023] [Accepted: 11/17/2023] [Indexed: 11/25/2023] Open

Sonam Dongsar T, Tsering Dongsar T, Molugulu N, Annadurai S, Wahab S, Gupta N, Kesharwani P. Targeted therapy of breast tumor by PLGA-based nanostructures: The versatile function in doxorubicin delivery. ENVIRONMENTAL RESEARCH 2023;233:116455. [PMID: 37356522 DOI: 10.1016/j.envres.2023.116455] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 06/15/2023] [Accepted: 06/17/2023] [Indexed: 06/27/2023]

Volmer LL, Önder CE, Volz B, Singh AR, Brucker SY, Engler T, Hartkopf AD, Koch A. Microfluidic Isolation of Disseminated Tumor Cells from the Bone Marrow of Breast Cancer Patients. Int J Mol Sci 2023;24:13930. [PMID: 37762233 PMCID: PMC10531360 DOI: 10.3390/ijms241813930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open

Welter L, Zheng S, Setayesh SM, Morikado M, Agrawal A, Nevarez R, Naghdloo A, Pore M, Higa N, Kolatkar A, Thiele JA, Sharma P, Moore HCF, Richer JK, Elias A, Pienta KJ, Zurita AJ, Gross ME, Shishido SN, Hicks J, Velasco CR, Kuhn P. Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics. Cancers (Basel) 2023;15:3949. [PMID: 37568766 PMCID: PMC10417732 DOI: 10.3390/cancers15153949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/14/2023] [Accepted: 07/21/2023] [Indexed: 08/13/2023] Open

Affiliation(s)

Lisa Welter Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.) Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA
Serena Zheng Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Sonia Maryam Setayesh Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.) Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA
Michael Morikado Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Arushi Agrawal Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Rafael Nevarez Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Amin Naghdloo Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.) Department of Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA
Milind Pore Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Nikki Higa Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.) Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Anand Kolatkar Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Jana-Aletta Thiele Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Priyanka Sharma University of Kansas Medical Center, Westwood, KS 66205, USA;
Halle C. F. Moore Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA;
Jennifer K. Richer University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (J.K.R.); (A.E.)
Anthony Elias University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (J.K.R.); (A.E.)
Kenneth J. Pienta The Cancer Ecology Center, Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA;
Amado J. Zurita Department of Genitourinary Medical Oncology, MD Anderson, Houston, TX 77230, USA;
Mitchell E. Gross Lawrence J. Ellison Institute for Transformative Medicine, Los Angeles, CA 90064, USA; Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA
Stephanie N. Shishido Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
James Hicks Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.) Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA
Carmen Ruiz Velasco Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.)
Peter Kuhn Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA; (L.W.); (S.Z.); (S.M.S.); (M.M.); (A.A.); (R.N.); (A.N.); (M.P.); (N.H.); (A.K.); (J.-A.T.); (S.N.S.); (C.R.V.) Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA Department of Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA Catherine & Joseph Aresty Department of Urology, Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

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Marcu LG, Moghaddasi L, Bezak E. Cannot Target What Cannot Be Seen: Molecular Imaging of Cancer Stem Cells. Int J Mol Sci 2023;24:ijms24021524. [PMID: 36675033 PMCID: PMC9864237 DOI: 10.3390/ijms24021524] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 12/29/2022] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open

Ni Z, Cao Y, Liu L, Huang C, Xie H, Zhou J, Ge B, Huang Q. Impact of endoscopic metallic stent placement and emergency surgery on detection of viable circulating tumor cells for acute malignant left-sided colonic obstruction. World J Surg Oncol 2023;21:1. [PMID: 36588150 PMCID: PMC9806888 DOI: 10.1186/s12957-022-02879-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 12/17/2022] [Indexed: 01/03/2023] Open

Ju S, Chen C, Zhang J, Xu L, Zhang X, Li Z, Chen Y, Zhou J, Ji F, Wang L. Detection of circulating tumor cells: opportunities and challenges. Biomark Res 2022;10:58. [PMID: 35962400 PMCID: PMC9375360 DOI: 10.1186/s40364-022-00403-2] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/26/2022] [Indexed: 11/25/2022] Open

Affiliation(s)

Siwei Ju Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Cong Chen Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Jiahang Zhang Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Lin Xu Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Xun Zhang Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Zhaoqing Li Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Yongxia Chen Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Jichun Zhou Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China
Feiyang Ji Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China. Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China.
Linbo Wang Department of Surgical Oncology, The Sir Run Run Shaw Hospital Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China. Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang, Hangzhou, China.

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Hu B, Gong Y, Wang Y, Xie J, Cheng J, Huang Q. Comprehensive Atlas of Circulating Rare Cells Detected by SE-iFISH and Image Scanning Platform in Patients With Various Diseases. Front Oncol 2022;12:821454. [PMID: 35311070 PMCID: PMC8924462 DOI: 10.3389/fonc.2022.821454] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/07/2022] [Indexed: 12/23/2022] Open

Abstract

Objective

Circulating rare cells (CRCs) are known as a crucial nucleated cellular response to pathological conditions, yet the landscape of cell types across a wide variety of diseases lacks comprehensive understanding. This study aimed at detecting and presenting a full spectrum of highly heterogeneous CRCs in clinical practice and further explored the characterization of CRC subtypes in distinct biomarker combinations and aneuploid chromosomes among various disease groups.

Methods

Peripheral blood was obtained from 2,360 patients with different cancers and non-neoplastic diseases. CRC capture and identification were accomplished using a novel platform integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy with a high-throughput automated image scanning system, on which hemocyte, tumor, epithelial, endothelial, mesenchymal, and stemness biomarkers were immunostained and displayed simultaneously. Double chromosome enumeration probe (CEP8 and CEP12) co-detection was performed on isolated CRCs from an extended trial for two chromosome ploidy patterns.

Results

A comprehensive atlas categorizing the diverse CRCs into 71 subtypes outlining was mapped out. The presence of epithelial-mesenchymal transition (EMT) or endothelial-mesenchymal transition (EndoMT), the cells with progenitor property, hematologic CRCs expressing multiple biomarkers, CRCs at "naked nuclei" status, and the rarely reported aneuploid mesenchymal epithelial-endothelial fusion cluster were described. Circulating tumor cells (CTCs) were detected in 2,157 (91.4%) patients; the total numbers of CTCs and circulating tumor-derived endothelial cells (CTECs) were relatively higher in several digestive system cancer types and non-neoplastic infectious diseases (p < 0.05). Co-detection combining CEP8 and CEP12 showed a higher diagnostic specificity on account of 57.27% false negativity of CRC detection through a single probe of CEP8.

Conclusions

The alternative biomarkers and chromosomes to be targeted by SE-iFISH and the image scanning platform, along with the comprehensive atlas, offer insight into the heterogeneity of CRCs and reveal potential contributions to specific disease diagnosis and therapeutic target cell discovery.

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Yadav A, Kumar A, Siddiqui MH. Detection of circulating tumour cells in colorectal cancer: Emerging techniques and clinical implications. World J Clin Oncol 2021;12:1169-1181. [PMID: 35070736 PMCID: PMC8716996 DOI: 10.5306/wjco.v12.i12.1169] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/15/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open

Kim H, Heo CM, Oh J, Chung HH, Lee EM, Park J, Lee SH, Lee KH, Lee KT, Lee JK, Cho YK, Park JK. Clinical significance of circulating tumor cells after chemotherapy in unresectable pancreatic ductal adenocarcinoma. Transl Oncol 2021;16:101321. [PMID: 34954457 PMCID: PMC8718659 DOI: 10.1016/j.tranon.2021.101321] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 12/14/2021] [Accepted: 12/16/2021] [Indexed: 12/01/2022] Open

Affiliation(s)

Hyemin Kim Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea; Medical Research Institute, Sungkyunkwan University School of Medicine, Seoul 06351 Republic of Korea
Chan Mi Heo Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
Jinmyeong Oh Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
Hwe Hoon Chung Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
Eun Mi Lee Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
Juhee Park Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea; Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Se-Hoon Lee Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea
Kwang Hyuck Lee Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
Kyu Taek Lee Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
Jong Kyun Lee Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
Yoon-Kyoung Cho Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea; Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
Joo Kyung Park Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea.

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Espejo-Cruz ML, González-Rubio S, Zamora-Olaya J, Amado-Torres V, Alejandre R, Sánchez-Frías M, Ciria R, De la Mata M, Rodríguez-Perálvarez M, Ferrín G. Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal. Int J Mol Sci 2021;22:ijms222313073. [PMID: 34884878 PMCID: PMC8657934 DOI: 10.3390/ijms222313073] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/27/2021] [Accepted: 11/30/2021] [Indexed: 02/07/2023] Open

Affiliation(s)

María Lola Espejo-Cruz Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
Sandra González-Rubio Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
Javier Zamora-Olaya Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.) Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
Víctor Amado-Torres Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.) Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
Rafael Alejandre Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.) Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
Marina Sánchez-Frías Department of Pathology, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain;
Rubén Ciria Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.) Department of Hepatobiliary Surgery and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain
Manuel De la Mata Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.) Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
Manuel Rodríguez-Perálvarez Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.) Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain Correspondence:
Gustavo Ferrín Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain

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Xie J, Ruan Z, Zheng J, Gong Y, Wang Y, Hu B, Cheng J, Huang Q. Detection of circulating rare cells benefitted the diagnosis of malignant solitary pulmonary nodules. J Cancer Res Clin Oncol 2021;148:2681-2692. [PMID: 34791530 DOI: 10.1007/s00432-021-03852-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 11/05/2021] [Indexed: 11/24/2022]

He S, Wei J, Ding L, Yang X, Wu Y. State-of-the-arts techniques and current evolving approaches in the separation and detection of circulating tumor cell. Talanta 2021;239:123024. [PMID: 34952370 DOI: 10.1016/j.talanta.2021.123024] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/29/2021] [Accepted: 10/30/2021] [Indexed: 01/01/2023]

Huang M, Ma Y, Lv C, Li S, Lu F, Zhang S, Wang DD, Lin PP, Yang Y. Aneuploid Circulating Tumor Cells as a Predictor of Response to Neoadjuvant Chemotherapy in Non-Small Cell Lung Cancer. Int J Gen Med 2021;14:6609-6620. [PMID: 34703281 PMCID: PMC8523810 DOI: 10.2147/ijgm.s330361] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 09/02/2021] [Indexed: 11/23/2022] Open

Pan M, Kohlbauer V, Blancke Soares A, Schinke H, Huang Y, Kranz G, Quadt T, Hachmeister M, Gires O. Interactome analysis reveals endocytosis and membrane recycling of EpCAM during differentiation of embryonic stem cells and carcinoma cells. iScience 2021;24:103179. [PMID: 34693227 PMCID: PMC8517208 DOI: 10.1016/j.isci.2021.103179] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 08/16/2021] [Accepted: 09/23/2021] [Indexed: 12/16/2022] Open

Zhang T, Zhang L, Gao Y, Wang Y, Liu Y, Zhang H, Wang Q, Hu F, Li J, Tan J, Wang DD, Gires O, Lin PP, Li B. Role of aneuploid circulating tumor cells and CD31⁺ circulating tumor endothelial cells in predicting and monitoring anti-angiogenic therapy efficacy in advanced NSCLC. Mol Oncol 2021;15:2891-2909. [PMID: 34455700 PMCID: PMC8564645 DOI: 10.1002/1878-0261.13092] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 08/23/2021] [Indexed: 12/18/2022] Open

Affiliation(s)

Tongmei Zhang Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Lina Zhang Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Yuan Gao Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Ying Wang Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Yanxia Liu Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Hongmei Zhang Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Qunhui Wang Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Fanbin Hu Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Jie Li Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Jinjing Tan Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
Daisy Dandan Wang Cytelligen, San Diego, CA, USA
Olivier Gires Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, LMU Munich, Germany
Peter Ping Lin Cytelligen, San Diego, CA, USA
Baolan Li Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China

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Pillai SG, Siddappa CM, Ma C, Snider J, Kaushal M, Watson MA, Aft R. A microfluidic-based filtration system to enrich for bone marrow disseminated tumor cells from breast cancer patients. PLoS One 2021;16:e0246139. [PMID: 33989287 PMCID: PMC8121342 DOI: 10.1371/journal.pone.0246139] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 01/13/2021] [Indexed: 01/07/2023] Open

Agnoletto C, Caruso C, Garofalo C. Heterogeneous Circulating Tumor Cells in Sarcoma: Implication for Clinical Practice. Cancers (Basel) 2021;13:cancers13092189. [PMID: 34063272 PMCID: PMC8124844 DOI: 10.3390/cancers13092189] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/29/2021] [Accepted: 04/30/2021] [Indexed: 12/12/2022] Open

Abstract

Simple Summary

The present review is aimed to discuss the relevance of assaying for the presence and isolation of circulating tumor cells (CTCs) in patients with sarcoma. Just a few studies have been performed to detect and enumerate viable CTCs in sarcoma and a majority of them still represent proof-of-concept studies, while more frequently tumor cells have been detected in the circulation by using the PCR-based method. Nevertheless, recent advances in technologies allowed detection of epithelial–mesenchymal transitioned CTCs from patients with mesenchymal malignancies, despite results being mostly preliminary. The possibility to identify CTCs holds a great promise for both applications of liquid biopsy in sarcoma for precision medicine, and for research purposes to pinpoint the mechanism of the metastatic process through the characterization of tumor mesenchymal cells. Coherently, clinical trials in sarcoma have been designed accordingly to detect CTCs, for diagnosis, identification of novel therapeutic targets and resistance mechanisms of systemic therapies, and patient stratification.

Abstract

Bone and soft tissue sarcomas (STSs) represent a group of heterogeneous rare malignant tumors of mesenchymal origin, with a poor prognosis. Due to their low incidence, only a few studies have been reported addressing circulating tumor cells (CTCs) in sarcoma, despite the well-documented relevance for applications of liquid biopsy in precision medicine. In the present review, the most recent data relative to the detection and isolation of viable and intact CTCs in these tumors will be reviewed, and the heterogeneity in CTCs will be discussed. The relevance of epithelial–mesenchymal plasticity and stemness in defining the phenotypic and functional properties of these rare cells in sarcoma will be highlighted. Of note, the existence of dynamic epithelial–mesenchymal transition (EMT)-related processes in sarcoma tumors has only recently been related to their clinical aggressiveness. Also, the presence of epithelial cell adhesion molecule (EpCAM)-positive CTC in sarcoma has been weakly correlated with poor outcome and disease progression, thus proving the existence of both epithelial and mesenchymal CTC in sarcoma. The advancement in technologies for capturing and enumerating all diverse CTCs phenotype originating from these mesenchymal tumors are presented, and results provide a promising basis for clinical application of CTC detection in sarcoma.

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Balázs K, Antal L, Sáfrány G, Lumniczky K. Blood-Derived Biomarkers of Diagnosis, Prognosis and Therapy Response in Prostate Cancer Patients. J Pers Med 2021;11:296. [PMID: 33924671 PMCID: PMC8070149 DOI: 10.3390/jpm11040296] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 03/31/2021] [Accepted: 04/03/2021] [Indexed: 12/11/2022] Open

Gires O, Pan M, Schinke H, Canis M, Baeuerle PA. Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years? Cancer Metastasis Rev 2020;39:969-987. [PMID: 32507912 PMCID: PMC7497325 DOI: 10.1007/s10555-020-09898-3] [Citation(s) in RCA: 197] [Impact Index Per Article: 39.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]

The Significance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma: Real-Time Monitoring and Moving Targets for Cancer Therapy. Cancers (Basel) 2020;12:cancers12071734. [PMID: 32610709 PMCID: PMC7408113 DOI: 10.3390/cancers12071734] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/26/2020] [Accepted: 06/27/2020] [Indexed: 02/08/2023] Open

Aneuploid Circulating Tumor-Derived Endothelial Cell (CTEC): A Novel Versatile Player in Tumor Neovascularization and Cancer Metastasis. Cells 2020;9:cells9061539. [PMID: 32599893 PMCID: PMC7349247 DOI: 10.3390/cells9061539] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/12/2020] [Accepted: 06/22/2020] [Indexed: 12/14/2022] Open

Abstract

Hematogenous and lymphogenous cancer metastases are significantly impacted by tumor neovascularization, which predominantly consists of blood vessel-relevant angiogenesis, vasculogenesis, vasculogenic mimicry, and lymphatic vessel-related lymphangiogenesis. Among the endothelial cells that make up the lining of tumor vasculature, a majority of them are tumor-derived endothelial cells (TECs), exhibiting cytogenetic abnormalities of aneuploid chromosomes. Aneuploid TECs are generated from “cancerization of stromal endothelial cells” and “endothelialization of carcinoma cells” in the hypoxic tumor microenvironment. Both processes crucially engage the hypoxia-triggered epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT). Compared to the cancerization process, endothelialization of cancer cells, which comprises the fusion of tumor cells with endothelial cells and transdifferentiation of cancer cells into TECs, is the dominant pathway. Tumor-derived endothelial cells, possessing the dual properties of cancerous malignancy and endothelial vascularization ability, are thus the endothelialized cancer cells. Circulating tumor-derived endothelial cells (CTECs) are TECs shed into the peripheral circulation. Aneuploid CD31⁺ CTECs, together with their counterpart CD31^- circulating tumor cells (CTCs), constitute a unique pair of cellular circulating tumor biomarkers. This review discusses a proposed cascaded framework that focuses on the origins of TECs and CTECs in the hypoxic tumor microenvironment and their clinical implications for tumorigenesis, neovascularization, disease progression, and cancer metastasis. Aneuploid CTECs, harboring hybridized properties of malignancy, vascularization and motility, may serve as a unique target for developing a novel metastasis blockade cancer therapy.

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Zou L, Imani S, Maghsoudloo M, Shasaltaneh MD, Gao L, Zhou J, Wen Q, Liu S, Zhang L, Chen G. Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis. Oncol Rep 2020;44:1075-1093. [PMID: 32705227 PMCID: PMC7388446 DOI: 10.3892/or.2020.7650] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 05/12/2020] [Indexed: 12/15/2022] Open

Abstract

The genome‑wide copy number analysis of circulating tumor cells (CTCs) provides a promising prognostic biomarker for survival in breast cancer liver metastasis (BCLM) patients. The present study aimed to confirm the prognostic value of the presence of CTCs in BCLM patients. We previously developed an assay for the genome‑wide pattern differences in copy number variations (CNVs) as an adjunct test for the routine imaging and histopathologic diagnosis methods to distinguish newly diagnosed liver metastases and recurrent liver metastases. Forty‑three breast cancer patients were selected for this study in which 23 newly diagnosed and 20 recurrent liver metastases were diagnosed by histopathology and 18F‑FDG PET/CT imaging. CTCs were counted from all patients using the CellSearch system and were confirmed by cytomorphology and three‑color immunocytochemistry. Genomic DNA of single CTCs was amplified using multiple annealing and looping based amplification cycles (MALBAC). Then, we compared the CTC numbers of newly diagnosed and recurrent BCLM patients using Illumina platforms. A high CTC frequency (>15 CTCs/7.5 ml blood) was found to be correlated with disease severity and metastatic progression, which suggests the value for CTCs in the diagnosis of BCLM in comparison with pathohistology and PET/CT imaging (P>0.05). Moreover, CTCs isolated from BCLM patients remained an independent prognostic detection factor associated with overall survival (P=0.0041). Comparison between newly diagnosed and recurrent liver metastases revealed different frequencies of CNVs (P>0.05). Notably, the CNV pattern of isolated CTCs of recurrent BCLM patients was similar to recurrent liver metastases (nearly 82% of the gain/loss regions). Functional enrichment analysis identified 25 genes as a CNV signature of BCLM. Among them, were defensin and β‑defensin genes, which are significantly associated with anti‑angiogenesis and immunomodulation signaling pathways. High CTC frequencies are effective in the evaluation and differentiation between newly diagnosed liver metastases from recurrent liver metastases. Future clinical studies will be necessary to fully determine the prognostic potential of CTC cluster signatures in patients with BCLM.

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Cui Z, Su F, Li Y, Yang D. Circulating tumour cells as prognosis predictive markers of neoadjuvant chemotherapy-treated breast cancer patients. J Chemother 2020;32:304-309. [PMID: 32500819 DOI: 10.1080/1120009x.2020.1774207] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]

Künzel J, Gribko A, Lu Q, Stauber RH, Wünsch D. Nanomedical detection and downstream analysis of circulating tumor cells in head and neck patients. Biol Chem 2020;400:1465-1479. [PMID: 30903749 DOI: 10.1515/hsz-2019-0141] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 03/14/2019] [Indexed: 12/27/2022]

Wu J, Raba K, Guglielmi R, Behrens B, Van Dalum G, Flügen G, Koch A, Patel S, Knoefel WT, Stoecklein NH, Neves RPL. Magnetic-Based Enrichment of Rare Cells from High Concentrated Blood Samples. Cancers (Basel) 2020;12:E933. [PMID: 32290064 PMCID: PMC7225976 DOI: 10.3390/cancers12040933] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 03/30/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022] Open

Affiliation(s)

Junhao Wu Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)
Katharina Raba Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany;
Rosa Guglielmi Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)
Bianca Behrens Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)
Guus Van Dalum Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)
Georg Flügen Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)
Andreas Koch Thermo Fisher Scientific, Postfach 200152, Frankfurter Str. 129B, 64293 Darmstadt, Germany;
Suraj Patel Thermo Fisher Scientific, 3 Fountain Drive, Inchinnan, Renfrew PA4 9RF, UK;
Wolfram T. Knoefel Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)
Nikolas H. Stoecklein Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)
Rui P. L. Neves Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; (J.W.); (R.G.); (B.B.); (G.V.D.); (G.F.); (W.T.K.)

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Mohtar MA, Syafruddin SE, Nasir SN, Yew LT. Revisiting the Roles of Pro-Metastatic EpCAM in Cancer. Biomolecules 2020;10:biom10020255. [PMID: 32046162 PMCID: PMC7072682 DOI: 10.3390/biom10020255] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/05/2020] [Accepted: 02/05/2020] [Indexed: 12/12/2022] Open

Zhang L, Zhang X, Liu Y, Zhang T, Wang Z, Gu M, Li Y, Wang DD, Li W, Lin PP. PD-L1+ aneuploid circulating tumor endothelial cells (CTECs) exhibit resistance to the checkpoint blockade immunotherapy in advanced NSCLC patients. Cancer Lett 2020;469:355-366. [DOI: 10.1016/j.canlet.2019.10.041] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 10/22/2019] [Accepted: 10/27/2019] [Indexed: 12/23/2022]

Wan S, Kim TH, Smith KJ, Delaney R, Park GS, Guo H, Lin E, Plegue T, Kuo N, Steffes J, Leu C, Simeone DM, Razimulava N, Parikh ND, Nagrath S, Welling TH. New Labyrinth Microfluidic Device Detects Circulating Tumor Cells Expressing Cancer Stem Cell Marker and Circulating Tumor Microemboli in Hepatocellular Carcinoma. Sci Rep 2019;9:18575. [PMID: 31819089 PMCID: PMC6901480 DOI: 10.1038/s41598-019-54960-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 11/21/2019] [Indexed: 02/07/2023] Open

Affiliation(s)

Shanshan Wan Perlmutter Cancer Center and Department of Surgery, NYU Langone Health, New York, NY, USA
Tae Hyun Kim Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA Biointerfaces Inst., University of Michigan, Ann Arbor, MI, USA
Kaylee J Smith Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA Biointerfaces Inst., University of Michigan, Ann Arbor, MI, USA
Ryan Delaney Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA
G-Su Park Department of Chemistry, University of Michigan, Ann Arbor, MI, USA
Hui Guo Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Eric Lin Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA Biointerfaces Inst., University of Michigan, Ann Arbor, MI, USA
Thomas Plegue Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA
Ning Kuo School of Medicine, University of Michigan, Ann Arbor, MI, USA
John Steffes School of Medicine, University of Michigan, Ann Arbor, MI, USA
Christopher Leu Perlmutter Cancer Center and Department of Surgery, NYU Langone Health, New York, NY, USA
Diane M Simeone Perlmutter Cancer Center and Department of Surgery, NYU Langone Health, New York, NY, USA
Nataliya Razimulava Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
Neehar D Parikh Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
Sunitha Nagrath Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. Biointerfaces Inst., University of Michigan, Ann Arbor, MI, USA. Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Theodore H Welling Perlmutter Cancer Center and Department of Surgery, NYU Langone Health, New York, NY, USA.

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EpCAM^low Circulating Tumor Cells: Gold in the Waste. DISEASE MARKERS 2019;2019:1718920. [PMID: 31636732 PMCID: PMC6766153 DOI: 10.1155/2019/1718920] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 09/06/2019] [Accepted: 09/11/2019] [Indexed: 12/14/2022]

Circulating biomarkers for early detection and clinical management of colorectal cancer. Mol Aspects Med 2019;69:107-122. [PMID: 31189073 DOI: 10.1016/j.mam.2019.06.002] [Citation(s) in RCA: 186] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 06/07/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023]

Liu X, Li J, Cadilha BL, Markota A, Voigt C, Huang Z, Lin PP, Wang DD, Dai J, Kranz G, Krandick A, Libl D, Zitzelsberger H, Zagorski I, Braselmann H, Pan M, Zhu S, Huang Y, Niedermeyer S, Reichel CA, Uhl B, Briukhovetska D, Suárez J, Kobold S, Gires O, Wang H. Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis. SCIENCE ADVANCES 2019;5:eaav4275. [PMID: 31223646 PMCID: PMC6584608 DOI: 10.1126/sciadv.aav4275] [Citation(s) in RCA: 129] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 05/15/2019] [Indexed: 05/21/2023]

Affiliation(s)

Xiao Liu Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Junjian Li Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Bruno Loureiro Cadilha Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany
Anamarija Markota Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany
Cornelia Voigt Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany
Zhe Huang Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Peter P. Lin Cytelligen, San Diego, CA 92121, USA
Daisy D. Wang Cytelligen, San Diego, CA 92121, USA
Juncheng Dai Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
Gisela Kranz Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Anna Krandick Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Darko Libl Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Horst Zitzelsberger Clinical Cooperation Group Personalized Radiotherapy of Head and Neck Tumors, Helmholtz Zentrum München, Neuherberg, Germany Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
Isabella Zagorski Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany
Herbert Braselmann Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany
Min Pan Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Sibo Zhu State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China
Yuanchi Huang Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Sebastian Niedermeyer Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Christoph A. Reichel Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Bernd Uhl Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Daria Briukhovetska Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany
Javier Suárez Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany
Sebastian Kobold Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, Department of Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Lindwurmstrasse 2a, 80337 Munich, Germany
Olivier Gires Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany Clinical Cooperation Group Personalized Radiotherapy of Head and Neck Tumors, Helmholtz Zentrum München, Neuherberg, Germany Corresponding author. (O.G.); (H.W.)
Hongxia Wang Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China Corresponding author. (O.G.); (H.W.)

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Mu W, Wang Z, Zöller M. Ping-Pong-Tumor and Host in Pancreatic Cancer Progression. Front Oncol 2019;9:1359. [PMID: 31921628 PMCID: PMC6927459 DOI: 10.3389/fonc.2019.01359] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 11/18/2019] [Indexed: 12/12/2022] Open

Abstract

Metastasis is the main cause of high pancreatic cancer (PaCa) mortality and trials dampening PaCa mortality rates are not satisfying. Tumor progression is driven by the crosstalk between tumor cells, predominantly cancer-initiating cells (CIC), and surrounding cells and tissues as well as distant organs, where tumor-derived extracellular vesicles (TEX) are of major importance. A strong stroma reaction, recruitment of immunosuppressive leukocytes, perineural invasion, and early spread toward the peritoneal cavity, liver, and lung are shared with several epithelial cell-derived cancer, but are most prominent in PaCa. Here, we report on the state of knowledge on the PaCIC markers Tspan8, alpha6beta4, CD44v6, CXCR4, LRP5/6, LRG5, claudin7, EpCAM, and CD133, which all, but at different steps, are engaged in the metastatic cascade, frequently via PaCIC-TEX. This includes the contribution of PaCIC markers to TEX biogenesis, targeting, and uptake. We then discuss PaCa-selective features, where feedback loops between stromal elements and tumor cells, including distorted transcription, signal transduction, and metabolic shifts, establish vicious circles. For the latter particularly pancreatic stellate cells (PSC) are responsible, furnishing PaCa to cope with poor angiogenesis-promoted hypoxia by metabolic shifts and direct nutrient transfer via vesicles. Furthermore, nerves including Schwann cells deliver a large range of tumor cell attracting factors and Schwann cells additionally support PaCa cell survival by signaling receptor binding. PSC, tumor-associated macrophages, and components of the dysplastic stroma contribute to perineural invasion with signaling pathway activation including the cholinergic system. Last, PaCa aggressiveness is strongly assisted by the immune system. Although rich in immune cells, only immunosuppressive cells and factors are recovered in proximity to tumor cells and hamper effector immune cells entering the tumor stroma. Besides a paucity of immunostimulatory factors and receptors, immunosuppressive cytokines, myeloid-derived suppressor cells, regulatory T-cells, and M2 macrophages as well as PSC actively inhibit effector cell activation. This accounts for NK cells of the non-adaptive and cytotoxic T-cells of the adaptive immune system. We anticipate further deciphering the molecular background of these recently unraveled intermingled phenomena may turn most lethal PaCa into a curatively treatable disease.

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Huang Y, Chanou A, Kranz G, Pan M, Kohlbauer V, Ettinger A, Gires O. Membrane-associated epithelial cell adhesion molecule is slowly cleaved by γ-secretase prior to efficient proteasomal degradation of its intracellular domain. J Biol Chem 2018;294:3051-3064. [PMID: 30598504 DOI: 10.1074/jbc.ra118.005874] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 12/20/2018] [Indexed: 12/27/2022] Open

Abstract

Regulated intramembrane proteolysis (RIP) is a key mechanism for activating transmembrane proteins such as epithelial cell adhesion molecule (EpCAM) for cellular signaling and degradation. EpCAM is highly expressed in carcinomas and progenitor and embryonic stem cells and is involved in the regulation of cell adhesion, proliferation, and differentiation. Strictly sequential cleavage of EpCAM through RIP involves initial shedding of the extracellular domain by α-secretase (ADAM) and β-secretase (BACE) sheddases, generating a membrane-tethered C-terminal fragment EpCTF. Subsequently, the rate-limiting γ-secretase complex catalyzes intramembrane cleavage of EpCTF, generating an extracellular EpCAM-Aβ-like fragment and an intracellular EpICD fragment involved in nuclear signaling. Here, we have combined biochemical approaches with live-cell imaging of fluorescent protein tags to investigate the kinetics of γ-secretase-mediated intramembrane cleavage of EpCTF. We demonstrate that γ-secretase-mediated proteolysis of exogenously and endogenously expressed EpCTF is a slow process with a 50% protein turnover in cells ranging from 45 min to 5.5 h. The slow cleavage was dictated by γ-secretase activity and not by EpCTF species, as indicated by cross-species swapping experiments. Furthermore, both human and murine EpICDs generated from EpCTF by γ-secretase were degraded efficiently (94-99%) by the proteasome. Hence, proteolytic cleavage of EpCTF is a comparably slow process, and EpICD generation does not appear to be suited for rapidly transducing extracellular cues into nuclear signaling, but appears to provide steady signals that can be further controlled through efficient proteasomal degradation. Our approach provides an unbiased bioassay to investigate proteolytic processing of EpCTF in single living cells.

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Rofi E, Vivaldi C, Del Re M, Arrigoni E, Crucitta S, Funel N, Fogli S, Vasile E, Musettini G, Fornaro L, Falcone A, Danesi R. The emerging role of liquid biopsy in diagnosis, prognosis and treatment monitoring of pancreatic cancer. Pharmacogenomics 2018;20:49-68. [PMID: 30520336 DOI: 10.2217/pgs-2018-0149] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open

High Expression of EpCAM and Sox2 is a Positive Prognosticator of Clinical Outcome for Head and Neck Carcinoma. Sci Rep 2018;8:14582. [PMID: 30275505 PMCID: PMC6167386 DOI: 10.1038/s41598-018-32178-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 08/29/2018] [Indexed: 01/06/2023] Open

Pan M, Schinke H, Luxenburger E, Kranz G, Shakhtour J, Libl D, Huang Y, Gaber A, Pavšič M, Lenarčič B, Kitz J, Jakob M, Schwenk-Zieger S, Canis M, Hess J, Unger K, Baumeister P, Gires O. EpCAM ectodomain EpEX is a ligand of EGFR that counteracts EGF-mediated epithelial-mesenchymal transition through modulation of phospho-ERK1/2 in head and neck cancers. PLoS Biol 2018;16:e2006624. [PMID: 30261040 PMCID: PMC6177200 DOI: 10.1371/journal.pbio.2006624] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 10/09/2018] [Accepted: 09/12/2018] [Indexed: 12/18/2022] Open

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are characterized by outstanding molecular heterogeneity that results in severe therapy resistance and poor clinical outcome. Inter- and intratumoral heterogeneity in epithelial-mesenchymal transition (EMT) was recently revealed as a major parameter of poor clinical outcome. Here, we addressed the expression and function of the therapeutic target epidermal growth factor receptor (EGFR) and of the major determinant of epithelial differentiation epithelial cell adhesion molecule (EpCAM) in clinical samples and in vitro models of HNSCCs. We describe improved survival of EGFR^low/EpCAM^high HNSCC patients (n = 180) and provide a molecular basis for the observed disparities in clinical outcome. EGF/EGFR have concentration-dependent dual capacities as inducers of proliferation and EMT through differential activation of the central molecular switch phosphorylated extracellular signal–regulated kinase 1/2 (pERK1/2) and EMT transcription factors (EMT-TFs) Snail, zinc finger E-box-binding homeobox 1 (Zeb1), and Slug. Furthermore, soluble ectodomain of EpCAM (EpEX) was identified as a ligand of EGFR that activates pERK1/2 and phosphorylated AKT (pAKT) and induces EGFR-dependent proliferation but represses EGF-mediated EMT, Snail, Zeb1, and Slug activation and cell migration. EMT repression by EpEX is realized through competitive modulation of pERK1/2 activation strength and inhibition of EMT-TFs, which is reflected in levels of pERK1/2 and its target Slug in clinical samples. Accordingly, high expression of pERK1/2 and/or Slug predicted poor outcome of HNSCCs. Hence, EpEX is a ligand of EGFR that induces proliferation but counteracts EMT mediated by the EGF/EGFR/pERK1/2 axis. Therefore, the emerging EGFR/EpCAM molecular cross talk represents a promising target to improve patient-tailored adjuvant treatment of HNSCCs.

Head and neck squamous cell carcinomas (HNSCCs) display poor survival, with death rates above 55%. Major factors affecting survival are metastases’ formation and therapy resistance. Phenotypic changes during partial epithelial-mesenchymal transition (EMT) provide tumor cells with increased migration, invasion, and therapy resistance. Understanding molecular mechanisms of EMT, as a central process of the metastatic cascade and the development of therapy resistance, is therefore important. In the present work, we identified molecular cross talk between epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) as a novel determinant of clinical outcome in HNSCCs. Low levels of EGFR but high levels of EpCAM (EGFR^low/EpCAM^high) were associated with favorable prognosis, with survival rates above 90%, whereas EGFR^high/EpCAM^low correlated with poor survival, below 10%. EGFR was shown to have a concentration-dependent capacity to induce proliferation and EMT. Proteolytic cleavage of the extracellular domain of EpCAM (EpEX) produces a ligand of EGFR that induces EGFR-dependent proliferation but counteracts EGF-induced EMT. We delineate an EGFR/extracellular signal–regulated kinase 1/2 (ERK1/2)/EpCAM signaling axis that may be a promising therapeutic target for HNSCCs.

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Affiliation(s)

Min Pan Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Henrik Schinke Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Elke Luxenburger Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Gisela Kranz Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Julius Shakhtour Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Darko Libl Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Yuanchi Huang Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Aljaž Gaber Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
Miha Pavšič Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
Brigita Lenarčič Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia Department of Biochemistry, Molecular and Structural Biology, Institute Jožef Stefan, Ljubljana, Slovenia
Julia Kitz Institute of Pathology, University Medical Center, Göttingen, Germany
Mark Jakob Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Sabina Schwenk-Zieger Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Martin Canis Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany
Julia Hess Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer“, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Neuherberg, Germany Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Neuherberg, Germany
Kristian Unger Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer“, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Neuherberg, Germany Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Neuherberg, Germany
Philipp Baumeister Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer“, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Neuherberg, Germany
Olivier Gires Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer“, Helmholtz Zentrum München, Research Center for Environmental Health (GmbH), Neuherberg, Germany * E-mail:

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Chen J, Shang B, Zhang H, Zhu Z, Chen L, Wang H, Ran F, Chen Q, Chen J. Enzyme-free ultrasensitive fluorescence detection of epithelial cell adhesion molecules based on a toehold-aided DNA recycling amplification strategy. RSC Adv 2018;8:14798-14805. [PMID: 35541343 PMCID: PMC9079946 DOI: 10.1039/c8ra01362d] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 04/04/2018] [Indexed: 01/13/2023] Open

Aneuploid CTC and CEC. Diagnostics (Basel) 2018;8:diagnostics8020026. [PMID: 29670052 PMCID: PMC6023477 DOI: 10.3390/diagnostics8020026] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 12/11/2022] Open

Circulating tumour cells in prostate cancer. Nat Rev Urol 2018;15:265-266. [DOI: 10.1038/nrurol.2018.25] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Sheng Y, Wang T, Li H, Zhang Z, Chen J, He C, Li Y, Lv Y, Zhang J, Xu C, Wang Z, Huang C, Wang L. Comparison of analytic performances of Cellsearch and iFISH approach in detecting circulating tumor cells. Oncotarget 2018;8:8801-8806. [PMID: 28187533 PMCID: PMC5352443 DOI: 10.18632/oncotarget.6688] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 12/10/2015] [Indexed: 01/06/2023] Open

Huebner H, Fasching PA, Gumbrecht W, Jud S, Rauh C, Matzas M, Paulicka P, Friedrich K, Lux MP, Volz B, Gass P, Häberle L, Meier-Stiegen F, Hartkopf A, Neubauer H, Almstedt K, Beckmann MW, Fehm TN, Ruebner M. Filtration based assessment of CTCs and CellSearch® based assessment are both powerful predictors of prognosis for metastatic breast cancer patients. BMC Cancer 2018;18:204. [PMID: 29463222 PMCID: PMC5819661 DOI: 10.1186/s12885-018-4115-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 02/09/2018] [Indexed: 12/17/2022] Open

Affiliation(s)

Hanna Huebner Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Peter A Fasching Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Walter Gumbrecht Siemens Healthcare GmbH, Günther-Scharowsky-Str.1, 91058, Erlangen, Germany
Sebastian Jud Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Claudia Rauh Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Mark Matzas Siemens Healthcare GmbH, Günther-Scharowsky-Str.1, 91058, Erlangen, Germany
Peter Paulicka Siemens Healthcare GmbH, Günther-Scharowsky-Str.1, 91058, Erlangen, Germany
Katja Friedrich Siemens Healthcare GmbH, Günther-Scharowsky-Str.1, 91058, Erlangen, Germany
Michael P Lux Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Bernhard Volz Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Paul Gass Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Lothar Häberle Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany.,Biostatistics Unit. Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Franziska Meier-Stiegen Department of Gynecology and Obstetrics, Heinrich Heine University of Düsseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
Andreas Hartkopf Department of Gynecology and Obstetrics, University Hospital Tuebingen, Calwerstraße 7, 72076, Tuebingen, Germany
Hans Neubauer Department of Gynecology and Obstetrics, Heinrich Heine University of Düsseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
Katrin Almstedt Department of Obstetrics and Gynecology, Johannes Gutenberg University, Langenbeckstrasse 1, 55131, Mainz, Germany
Matthias W Beckmann Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany
Tanja N Fehm Department of Gynecology and Obstetrics, Heinrich Heine University of Düsseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
Matthias Ruebner Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Universitaetsstraße 21-23, 91054, Erlangen, Germany.

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Wang H, Stoecklein NH, Lin PP, Gires O. Circulating and disseminated tumor cells: diagnostic tools and therapeutic targets in motion. Oncotarget 2018;8:1884-1912. [PMID: 27683128 PMCID: PMC5352105 DOI: 10.18632/oncotarget.12242] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 09/20/2016] [Indexed: 12/16/2022] Open

Gao F, Cui Y, Jiang H, Sui D, Wang Y, Jiang Z, Zhao J, Lin S. Circulating tumor cell is a common property of brain glioma and promotes the monitoring system. Oncotarget 2018;7:71330-71340. [PMID: 27517490 PMCID: PMC5342081 DOI: 10.18632/oncotarget.11114] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 07/10/2016] [Indexed: 11/29/2022] Open

Affiliation(s)

Faliang Gao Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, China
Yong Cui Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, China
Haihui Jiang Department of Neurosurgery, First Hospital of Tsinghua University, Beijing, China
Dali Sui Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, China
Yonggang Wang Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, China
Zhongli Jiang Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, China
Jizong Zhao Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, China
Song Lin Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Institute for Brain Disorders and Beijing Key Laboratory of Brian Tumor, Beijing, China

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Kuai JH, Wang Q, Zhang AJ, Zhang JY, Chen ZF, Wu KK, Hu XZ. Epidermal growth factor receptor-targeted immune magnetic liposomes capture circulating colorectal tumor cells efficiently. World J Gastroenterol 2018;24:351-359. [PMID: 29391757 PMCID: PMC5776396 DOI: 10.3748/wjg.v24.i3.351] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 11/27/2017] [Accepted: 12/04/2017] [Indexed: 02/06/2023] Open

Minimal Residual Disease in Head and Neck Cancer and Esophageal Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018;1100:55-82. [DOI: 10.1007/978-3-319-97746-1_4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]