Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression

Arun Satelli, Abhisek Mitra, Zachary Brownlee, Xueqing Xia, Seth Bellister, Michael J. Overman, Scott Kopetz, Lee M. Ellis, Qing H. Meng, Shulin Li

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Purpose: This study aimed to detect cell-surface vimentin (CSV) on the surface of epithelial-mesenchymal transitioned (EMT) circulating tumor cells (CTC) from blood of patients with epithelial cancers. Experimental Design: In this study, 101 patients undergoing postsurgery adjuvant chemotherapy for metastatic colon cancer were recruited. EMT CTCs were detected from blood of patients using the 84-1 monoclonal antibody against CSV as a marker. EMT CTCs isolated were characterized further using EMT-specific markers, fluorescent in situ hybridization, and single-cell mutation analysis. Results: Using the 84-1 antibody, we detected CSV exclusively on EMT CTCs from a variety of tumor types but not in the surrounding normal cells in the blood. The antibody exhibited very high specificity and sensitivity toward different epithelial cancer cells. With this antibody, we detected and enumerated EMT CTCs from patients. From our observations, we defined a cutoff of <5 or ≥5 EMT CTCs as the optimal threshold with respect to therapeutic response using ROC curves. Using this defined threshold, the presence of ≥5 EMT CTCs was associated with progressive disease, whereas patients with <5 EMT CTCs showed therapeutic response. Conclusion: Taken together, the number of EMT CTCs detected correlated with the therapeutic outcome of the disease. These results establish CSV as a universal marker for EMT CTCs from a wide variety of tumor types and thus provide the foundation for emerging CTC detection technologies and for studying the molecular regulation of these EMT CTCs.

Original languageEnglish (US)
Pages (from-to)899-906
Number of pages8
JournalClinical Cancer Research
Volume21
Issue number4
DOIs
StatePublished - Feb 15 2015
Externally publishedYes

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Circulating Neoplastic Cells
Vimentin
Neoplasms
Antibodies
Single-Cell Analysis
Adjuvant Chemotherapy
Fluorescence In Situ Hybridization
ROC Curve
Colonic Neoplasms
Blood Cells
Research Design
Therapeutics
Epithelial Cells
Monoclonal Antibodies
Technology
Sensitivity and Specificity
Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression. / Satelli, Arun; Mitra, Abhisek; Brownlee, Zachary; Xia, Xueqing; Bellister, Seth; Overman, Michael J.; Kopetz, Scott; Ellis, Lee M.; Meng, Qing H.; Li, Shulin.

In: Clinical Cancer Research, Vol. 21, No. 4, 15.02.2015, p. 899-906.

Research output: Contribution to journalArticle

Satelli, A, Mitra, A, Brownlee, Z, Xia, X, Bellister, S, Overman, MJ, Kopetz, S, Ellis, LM, Meng, QH & Li, S 2015, 'Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression', Clinical Cancer Research, vol. 21, no. 4, pp. 899-906. https://doi.org/10.1158/1078-0432.CCR-14-0894
Satelli, Arun ; Mitra, Abhisek ; Brownlee, Zachary ; Xia, Xueqing ; Bellister, Seth ; Overman, Michael J. ; Kopetz, Scott ; Ellis, Lee M. ; Meng, Qing H. ; Li, Shulin. / Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 4. pp. 899-906.
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