scholarly journals Circulating Tumor Cell Enumeration with a Combination of Epithelial Cell Adhesion Molecule– and Cell-Surface Vimentin–Based Methods for Monitoring Breast Cancer Therapeutic Response

2015 ◽  
Vol 61 (1) ◽  
pp. 259-266 ◽  
Author(s):  
Arun Satelli ◽  
Zachary Brownlee ◽  
Abhisek Mitra ◽  
Qing H Meng ◽  
Shulin Li

Abstract BACKGROUND Detection, isolation, and enumeration of circulating tumor cells (CTCs) from cancer patients has become an important modality in clinical management of patients with breast cancer. Although CellSearch, an epithelial cell adhesion molecule (EpCAM)-based method that is used to isolate epithelial CTCs, has gained prominence, its inability to detect mesenchymal CTCs from breast cancer patients raises concerns regarding its utility in clinical management. METHODS To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma tumors. In the present study, we tested the sensitivity and specificity of detecting CTCs from blood collected at a random time during therapy from each of 58 patients with metastatic breast cancer by use of 84-1 (a monoclonal antibody against CSV to detect epithelial/mesenchymal-transition CTCs) and CellSearch methods. Additionally, we tested the possibility of improving the sensitivity and specificity of detection by use of additional parameters including nuclear EpCAM localization and epithelial mesenchymal ratios. RESULTS CTC counts with CSV were significant (P = 0.0053) in differentiating populations responsive and nonresponsive to treatment compared with CTC counts with CellSearch (P = 0.0564). The specificity of CTC detection was found to be highest when the sum of CTC counts from the 2 methods was above a threshold of 8 CTCs/7.5 mL. CONCLUSIONS The sum of CTC counts from the CellSearch and CSV methods appears to provide new insights for assessment of therapeutic response and thus provides a new approach to personalized medicine in breast cancer patients.

Author(s):  
Katya Hekimian ◽  
Ernst-Ludwig Stein ◽  
Ulrich Pachmann ◽  
Katharina Pachmann

AbstractThe epithelial cell adhesion molecule (EpCAM) embedded in the plasma membrane of circulating epithelial tumor cells (CETC) is used for detection and enrichment of circulating tumor cells in peripheral blood and as a target for anti-epithelial antibodies elicited during immune response in anti-tumor immunization. Although an efficient immune response against EpCAM can be generated, the clinical application of such approaches has not been successful so far and the detection of circulating epithelial cells is highly variable. One reason for these discrepancies may be that not all circulating tumor cells are equally accessible for the specific antibody. A possible reason might be masking of EpCAM by glycoproteins or membrane lipoproteins preventing antibody binding.We have tested the application of detergents as demasking agents known to be successful in demasking red blood cell epitopes and determined how and in which way they affect integral membrane proteins and membrane lipids.The results showed that the polysorbate TweenThe data presented in this study suggest that EpCAM is present on part of circulating tumor cells in a masked form and that it is possible to demask EpCAM on CETC of breast cancer patients using Tween


2009 ◽  
Vol 123 (3) ◽  
pp. 701-708 ◽  
Author(s):  
Ashley Cimino ◽  
Marc Halushka ◽  
Peter Illei ◽  
Xinyan Wu ◽  
Saraswati Sukumar ◽  
...  

2009 ◽  
Vol 69 (3) ◽  
pp. 753-757 ◽  
Author(s):  
Narendra V. Sankpal ◽  
Michael W. Willman ◽  
Timothy P. Fleming ◽  
John D. Mayfield ◽  
William E. Gillanders

2008 ◽  
Vol 14 (18) ◽  
pp. 5849-5855 ◽  
Author(s):  
Marcus Schmidt ◽  
Dirk Hasenclever ◽  
Mitra Schaeffer ◽  
Daniel Boehm ◽  
Cristina Cotarelo ◽  
...  

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10777
Author(s):  
Yang Gao ◽  
Wan-Hung Fan ◽  
Zhengbo Song ◽  
Haizhou Lou ◽  
Xixong Kang

Purpose Status of epithelial-mesenchymal transition (EMT) varies from tumors to tumors. Epithelial cell adhesion molecule (EpCAM) and cell surface vimentin (CSV) are the most common used targets for isolating epithelial and mesenchymal CTCs, respectively. This study aimed to identify a suitable CTC capturing antibody for CTC enrichment in each solid tumor by comparing CTC detection rates with EpCAM and CSV antibodies in different solid tumors. Methods Treatment-naive patients with confirmed cancer diagnosis and healthy people who have performed CTC detection between April 2017 and May 2018 were included in this study. CTC detection was performed with CytoSorter® CTC system using either EpCAM or CSV antibody. In total, 853 CTC results from 690 cancer patients and 72 healthy people were collected for analysis. The performance of CTC capturing antibody was determined by the CTC detection rate. Results EpCAM has the highest CTC detection rate of 84.09% in CRC, followed by BCa (78.32%). CTC detection rates with EpCAM antibody are less than 40% in HCC (25%), PDAC (32.5%) and OC (33.33%). CSV has the highest CTC detection rate of 90% in sarcoma, followed by BC (85.71%), UC (84.62%), OC (83.33%) and BCa (81.82%). CTC detection rates with CSV antibody are over 60% in all 14 solid tumors. Except for CRC, CSV has better performances than EpCAM in most solid tumors regarding the CTC detection rates. Conclusion EpCAM can be used as a target to isolate CTCs in CRC, LC, GC, BCa, EC, HNSCC, CC and PCa, especially in CRC, while CSV can be used in most solid tumors for isolating CTCs.


Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769597 ◽  
Author(s):  
Dandan Zhang ◽  
Xue Liu ◽  
Jiujiao Gao ◽  
Yan Sun ◽  
Tingjiao Liu ◽  
...  

Glycosylation of cell surface proteins plays an important role in the regulation of apoptosis. It has been demonstrated that knockdown of epithelial cell adhesion molecule promoted apoptosis, inhibited cell proliferation, and caused cell-cycle arrest. In this study, we investigated whether and how N-glycosylation of epithelial cell adhesion molecule influenced the apoptosis in breast cancer cells. We applied the N-glycosylation mutation epithelial cell adhesion molecule plasmid to express deglycosylation of epithelial cell adhesion molecule and then to study its function. Our results showed that deglycosylation of epithelial cell adhesion molecule promoted apoptosis and inhibited cell proliferation. Deglycosylation of epithelial cell adhesion molecule enhanced the cytotoxic effect of 5-fluorouracil, promoting apoptosis by downregulating the expression of the anti-apoptotic protein Bcl-2 and upregulating the expression of the pro-apoptotic proteins Bax and Caspase 3 via the extracellular-signal-regulated kinase 1/2 and c-Jun N-terminal kinase mitogen-activated protein kinase signaling pathways in MCF-7 and MDA-MB-231 cells. These findings are important for a better understanding of epithelial cell adhesion molecule apoptosis regulation and suggest epithelial cell adhesion molecule as a potential target for the treatment of breast cancer.


Sign in / Sign up

Export Citation Format

Share Document