Minamiguchi Kazuhisa, Kawada Manabu, Someno Tetsuya, Ishizuka Masaaki
Institute for Chemotherapy, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, 410-0301, Shizuoka-ken, Japan.
Biochem Biophys Res Commun. 2003 Jul 4;306(3):629-36. doi: 10.1016/s0006-291x(03)01023-4.
Imbalances in the epithelial-stromal interactions are important in the pathogenesis of prostate cancer. However, we know little about androgenic regulation in the stroma of prostate cancer. We examined the cancer-stromal interaction paying attention to androgen responsiveness of stromal side. In co-culture, PC3 and LNCaP cells did not affect dihydrotestosterone (DHT)-dependent growth of prostate stromal cells (PrSCs), but DU145 cells significantly reduced it. Conditioned medium from DU145 cells (DU145-CM) also inhibited DHT-dependent PrSCs growth, androgen receptor (AR) expression, and prostate specific antigen transcription. Although the inhibitory effect of DU145-CM was not affected by neutralizing antibody against EGF, FGF-2, or TNF-alpha, pretreatment with testosterone-Sepharose partially reduced the inhibitory ability of DU145-CM. These results suggest that DU145 cells produce inhibitory factors for androgen responsiveness, including steroid-binding protein(s), and these may participate in crosstalk between DU145 cells and PrSCs as modulators of androgen.
上皮-基质相互作用的失衡在前列腺癌的发病机制中具有重要意义。然而，我们对前列腺癌基质中的雄激素调节知之甚少。我们研究了癌-基质相互作用，重点关注基质侧的雄激素反应性。在共培养中，PC3和LNCaP细胞不影响前列腺基质细胞（PrSCs）依赖二氢睾酮（DHT）的生长，但DU145细胞显著降低了其生长。来自DU145细胞的条件培养基（DU145-CM）也抑制了依赖DHT的PrSCs生长、雄激素受体（AR）表达以及前列腺特异性抗原转录。尽管DU145-CM的抑制作用不受针对表皮生长因子（EGF）、成纤维细胞生长因子-2（FGF-2）或肿瘤坏死因子-α（TNF-α）的中和抗体影响，但用睾酮-琼脂糖预处理可部分降低DU145-CM的抑制能力。这些结果表明，DU145细胞产生包括类固醇结合蛋白在内的雄激素反应性抑制因子，并且这些因子可能作为雄激素调节剂参与DU145细胞与PrSCs之间的相互作用。
