Department of Urology, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, 20 Yuhuangding Donglu, Yantai, Shandong Province 264000, China.
Med Oncol. 2013;30(3):674. doi: 10.1007/s12032-013-0674-9. Epub 2013 Aug 8.
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.
雄激素和雄激素受体(AR)通过上皮-间质相互作用在前列腺癌(PCa)的发展和进展中发挥关键作用。前列腺癌相关成纤维细胞(CAFs)是 PCa 基质中的主要成分,通过支持肿瘤发生和转移,在恶性进展中至关重要。然而,AR 在 CAFs 中的作用仍不清楚。我们从人 PCa 组织中分离并永生化 CAFs,发现 CAFs 为 AR 阳性。然后,我们用 siRNA 敲低其 AR,并将所得 CAFs 与 PCa 细胞系 PC3 共培养。通过 MTT、侵袭和集落形成测定来研究 PC3 的生物学行为。结果表明,敲低 CAFs 的 AR 后,PCa 上皮生长、侵袭和集落形成能力下降。通过实时定量聚合酶链反应,我们发现 AR 敲低的 CAFs 中 IGF1、FGF7、FGF10、SDF1、HGF 和 TGFb2 的表达水平降低。这些结果表明,AR 在 CAFs 中通过调节一系列生长因子促进 PCa 上皮生长和侵袭。针对 CAFs 中的 AR 可能是未来治疗 PCa 的潜在选择。