Interleukin‐6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation

作者：Kenichiro Ishii, Takeshi Sasaki, Kazuhiro Iguchi, Shinya Kajiwara, Manabu Kato, Hideki Kanda, YOSHIFUMI S. HIROKAWA, Kiminobu Arima, Atsushi Mizokami, Yoshiki Sugimura · 发表于：The Prostate · 年份：2018 · DOI：10.1002/pros.23643 · 被引用次数：34 · 研究领域：Prostate Cancer Treatment and Research、Chemokine receptors and signaling、Cancer, Stress, Anesthesia, and Immune Response

BACKGROUND: The reduced androgen-sensitivity of prostate cancer (PCa) cells is an important clinical development because of its association with the cells' progression to castration-resistant prostate cancer (CRPC). During androgen deprivation therapy (ADT), stroma-derived growth factors and cytokines can activate the androgen receptor (AR). For example, IL-6 is a multifunctional cytokine that is involved in the malignancy of PCa cells through AR activation. In the present study, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines to investigate the relationship between the responsiveness of PCa cells to IL-6 treatment and the cellular AR signaling pathway. METHODS: The androgen-low-sensitive F10 and E9 cells were obtained from LNCaP cells by limiting dilution method in regular culture condition. In contrast, the androgen-insensitive AIDL cells were established from LNCaP cells by continuous passaging in hormone-depleted condition. Original carcinoma-associated fibroblasts (CAFs) PCaSC-8 and PCaSC-9 cells were isolated from needle biopsy samples of PCa patients. RESULTS: In fibroblasts derived from PCa patients, IL-6 secretion was generally higher than that observed with normal fibroblasts. In contrast, IL-6 secretion was not detected in LNCaP and its sublines. The soluble IL-6 receptor was detected in PCa cells but not in fibroblasts. IL-6 treatment suppressed cell growth of LNCaP, F10, and E9 cells but not AIDL cells and it was accompanied with neuroe...