EMT circulating tumor cells detected by cell-surface vimentin are associated with prostate cancer progression.

Arun Satelli,Shouhao Zhou,Izhar Batth,Shulin Li,Qing H Meng,Heming Li,Christina R Rojas,Hyangsoon Noh,Zachary Brownlee,Abhishek Mitra

doi:10.18632/oncotarget.17632

Arun Satelli, Shouhao Zhou + Show 8 more

Open Access

https://doi.org/10.18632/oncotarget.17632

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Abstract

Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs. 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, breast, and colon cancer. Here we studied peripheral blood samples of 48 prostate cancer (PCA) patients including hormone sensitive and castration resistant sub-groups. Blood samples were analyzed for three different properties including our own CSV-based CTC enumeration (using 84-1 mAb against CSV), CellSearch-based epithelial CTC counts, and serum prostate-specific antigen (PSA) quantification. Our data demonstrated that in comparison with CellSearch, the CSV-based method had greater sensitivity and specificity. Further, we observed significantly greater numbers of CTCs in castration resistant patients as measured by our CSV method but not CellSearch. Our data suggests CSV-guided CTC enumeration may hold prognostic value and should be further validated as a possible measurement of PCA progression towards the deadly, androgen-independent form.

Highlights

Prostate cancer (PCA) is the second leading cause of death of men in the United States [1]
It is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like circulating tumor cells (CTC). To address this gap in technology, we recently discovered the utility of cellsurface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma, breast, and colon cancer
Since sarcoma cells are of mesenchymal origin and share a common phenotype with EMT cells, we explored the possibility of detecting EMT-like CTCs using 84-1 mAb against cell-surface vimentin (CSV) in prostate cancer (PCA) patients

Summary

Introduction

Prostate cancer (PCA) is the second leading cause of death of men in the United States [1]. In spite of these statistics, a valid and highly reliable means of predicting its progression towards androgen-independence has not yet been developed. In a landmark study conducted by Andriole et al which included over 70,000 men, the authors found that mortality due to PCA was not significantly reduced by the incorporation of regular PSA screenings [2]. Recent research further indicates that PSA may not be effective in differentiating between low-risk and aggressive types of PCA [3]. The identification and validation of biomarkers that can better diagnose PCA disease progression and assess its severity are critically needed

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