Tumor-Promoting Phenotype of CD90hi Prostate Cancer-Associated Fibroblasts

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Abstract

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.

CD90hi and CD90lo 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 CD90hi cells were MSCs. However, CD90hi 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 CD90hi 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 CD90hi 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.

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