Circulating fibroblast‐like cells in men with metastatic prostate cancer

Abstract

Metastatic prostate cancer is an incurable disease. During the development of this disease, prostate cancer cells enter the bloodstream as single cells or clusters of cells. Prostate fibroblasts, a cancer-promoting cell type in the prostate cancer microenvironment, could in theory incorporate into these migrating cell clusters or follow cancer cells into the bloodstream through holes in the tumor vasculature. Based on this idea, we hypothesized that fibroblast-like cells, defined here as cytokeratin 8/18/19(-) /DAPI(+) /CD45(-) /vimentin(+) cells, are present in the blood of men with metastatic prostate cancer. Veridex's CellSearch® system was used to immunomagnetically capture EpCAM(+) cells and clusters of cells heterogeneous for EpCAM expression from the blood of men with metastatic prostate cancer, localized cancer, and no known cancer, and immunostain them for the presence of cytokeratins 8/18/19, a nucleus, CD45, and vimentin. Fibroblast-like cells were then quantified. Fibroblast-like cells were present in 58.3% of men with metastatic prostate cancer but not in any men with localized prostate cancer or no known cancer. The presence of these cells correlated with certain known indicators of poor prognosis: ≥ 5 circulating tumor cells, defined here as cytokeratin 8/18/19(+) /DAPI(+) /CD45(-) cells, per 7.5 ml of blood, and a relatively high serum prostate-specific antigen level of ≥ 20 ng/ml. The presence of fibroblast-like cells in the blood may provide prognostic information as well as information about the biology of metastatic prostate cancer.