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

// Arun Satelli 1, * , Izhar Batth 1, * , Zachary Brownlee 1 , Abhishek Mitra 1 , Shouhao Zhou 2 , Hyangsoon Noh 1 , Christina R. Rojas 1 , Heming Li 1 , Qing H. Meng 3 and Shulin Li 1 1 Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3 Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA * These authors contributed equally to this work Correspondence to: Shulin Li, email: sli4@mdanderson.org Qing H. Meng, email: qhmeng@mdanderson.org Keywords: prostate cancer, epithelial mesenchymal transition, circulating tumor cells, vimentin, castration resistance Received: April 28, 2016 Accepted: April 21, 2017 Published: May 04, 2017 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.