Abstract
The androgens and androgen receptor (AR) play key roles in the prostate cancer (PCa) development and progression via epithelium-stroma cross talk. Prostate cancer-associated fibroblasts (CAFs) are dominant components in PCa stroma and are essential in the malignant progression by supporting tumorigenesis and metastasis. However, the AR roles in CAFs are still obscure. We isolated and immortalized the CAFs from human PCa tissues and found the CAFs are AR positive. We then knocked down their AR with siRNA and co-cultured the resultant CAFs with PCa cell line PC3. The MTT, invasion, and colony formation assays were performed to study the PC3 biological behavior. The results showed that the PCa epithelial growth, invasion, and colony formation abilities decreased when knocking down the CAFs AR. By using the real-time quantitative polymerase chain reaction, we found the IGF1, FGF7, FGF10, SDF1, HGF, and TGFb2 expression levels decreased in the AR knocked down CAFs. These results suggested that the AR in CAFs promoted PCa epithelial growth and invasion via regulating a series of growth factors. Targeting the AR in CAFs might be a potential therapeutic option for PCa in future.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Cell Line, Tumor
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Chemokine CXCL12 / genetics
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Chemokine CXCL12 / metabolism
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Disease Progression
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Epithelial Cells / metabolism
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Epithelial Cells / pathology*
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Fibroblast Growth Factor 10 / genetics
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Fibroblast Growth Factor 10 / metabolism
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Fibroblast Growth Factor 7 / genetics
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Fibroblast Growth Factor 7 / metabolism
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Fibroblasts / metabolism
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Fibroblasts / pathology*
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Hepatocyte Growth Factor / genetics
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Hepatocyte Growth Factor / metabolism
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Humans
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism
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Male
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Neoplasm Invasiveness / genetics
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Neoplasm Invasiveness / pathology*
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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Receptors, Androgen / genetics*
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Receptors, Androgen / metabolism*
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Transforming Growth Factor beta2 / genetics
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Transforming Growth Factor beta2 / metabolism
Substances
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AR protein, human
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CXCL12 protein, human
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Chemokine CXCL12
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FGF10 protein, human
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FGF7 protein, human
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Fibroblast Growth Factor 10
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HGF protein, human
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IGF1 protein, human
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Receptors, Androgen
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TGFB2 protein, human
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Transforming Growth Factor beta2
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Fibroblast Growth Factor 7
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Hepatocyte Growth Factor
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Insulin-Like Growth Factor I