Androgen receptor in cancer-associated fibroblasts influences stemness in cancer cells.
Androgen receptor in cancer-associated fibroblasts influences stemness in cancer cells.
复制标题
DOI：
10.1530/erc-16-0138
复制
发表时间：
2017-04
影响因子：
3.9
通讯作者：
Gross ME
中科院分区：
文献类型：
--
作者：
Liao CP;Chen LY;Luethy A;Kim Y;Kani K;MacLeod AR;Gross ME
Androgen receptor (AR) regulation pathways are essential for supporting the growth and survival of prostate cancer cells. Recently, sub-populations of prostate cancer cells have been identified with stem cell features and are associated with the emergence of treatment-resistant prostate cancer. Here, we explored the function of AR in prostate cancer-associated fibroblasts (CAFs) relative to growth and stem-cell associated characteristics. CAFs were isolated from the murine cPten−/− L prostate cancer model and cultured with human prostate cancer epithelial (hPCa) cells. A murine-specific AR antisense oligonucleotide (ASO) was used to suppress expression of AR in the CAF cells. CAFs express low, but significant levels of AR relative to fibroblasts derived from non-malignant tissue. CAFs promoted growth and colony formation of hPCa cells which was attenuated by suppression of AR expression. Surprisingly, AR-depleted CAFs promoted increased stem cell marker expression in hPCa cells. Interferon gamma (IFN-γ) and macrophage colony stimulating factor (M-CSF) were increased in AR-depleted CAF cells and exhibited similar effects on stem cell marker expression as seen in the CAF co-culture systems. Clinically, elevated IFN-γ expression was found to correlate with histologic grade in primary prostate cancer samples. In summary, AR and androgen-dependent signaling is active in CAFs and exerts significant effects on prostate cancer cells. IFN-γ and M-CSF are AR-regulated factors secreted by CAF cells which promote expression of stem cell markers in prostate cancer epithelial cells. Understanding how CAFs and other constituents of stromal tissue react to anti-cancer therapies may provide insight into the development and progression of prostate cancer.
