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Tumor‐promoting phenotype of CD90 hi prostate cancer‐associated fibroblasts
Author(s) -
Zhao Hongjuan,
Peehl Donna M.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20946
Subject(s) - cd90 , mesenchymal stem cell , stromal cell , cancer research , prostate cancer , biology , cancer , prostate , stroma , tumor progression , pathology , stem cell , medicine , immunology , microbiology and biotechnology , immunohistochemistry , cd34 , genetics
BACKGROUND Cancer‐associated stroma contributes to the malignant behavior of adenocarcinomas of the prostate and other organs. CD90 is a marker of mesenchymal stem cells (MSCs) and its expression is higher in prostate cancer stroma compared to normal tissue. Cultured prostate cancer‐associated fibroblasts (CAFs) expressing high versus low levels of CD90 were analyzed for an MSC‐like or tumor‐promoting phenotype. METHODS CD90 hi and CD90 lo cells were collected by fluorescence‐activated cell sorting (FACS). Expression of genes associated with MSCs and/or tumor‐promoting activities was measured by quantitative polymerase chain reaction (qPCR). Effects of stromal cell co‐culture or conditioned media were tested on BPH‐1 epithelial cells. RESULTS The pattern of gene expression did not support the hypothesis that CD90 hi cells were MSCs. However, CD90 hi cells expressed higher levels of many genes associated with tumor promotion, including cytokines, angiogenic factors, hedgehog signaling components, and transforming growth factor (TGF)‐β. Co‐culture or conditioned medium from CD90 hi cells increased CXCR4 expression in BPH‐1 cells, at least in part due to TGF‐β, and protected BPH‐1 cells from apoptosis. CONCLUSIONS Our results suggest that the elevated expression of CD90 previously observed in the cancer‐associated stroma of the human prostate is biologically significant. Although our results do not support the idea that CD90 hi cells cultured from the cancer stroma are MSCs, our findings suggest that the phenotype of these cells is more tumor‐promoting than that of cells expressing low CD90. Prostate 69: 991–1000, 2009. © 2009 Wiley‐Liss, Inc.