Neuroendocrine‐derived peptides promote prostate cancer cell survival through activation of IGF‐1R signaling

摘要: BACKGROUND Neuroendocrine (NE) cells promote the progression of prostate cancer to a castration-resistant state through production paracrine growth factors. We have demonstrated this principle using in vitro and vivo proliferative endpoints; however, contributions NE-derived pro-survival factors anti-apoptosis phenomenon not been thoroughly investigated. METHODS Here, we utilized conditioned-medium (CM) from LNCaP cells, engineered undergo NE differentiation, examined its effects on PC3 cell survival. RESULTS Statistically significant changes clonogenic survival, Annexin V staining, PARP cleavage trypan blue positivity approximately twofold were observed presence CM relative control-CM for both cells. These partially abrogated by antagonists neuropeptides neurotensin, bombesin, PTHrP. Selective inhibitors IGF-1R, EGFR or Src caused nearly complete blockade survival due secretions. Similar increases treated with medium docetaxel. Increased phosphorylation following treatment medium, was accompanied decreased protein tyrosine phosphatase, receptor type F (PTPRF) mRNA, levels. Overexpression PTPRF amplitude duration IGF-1R phosphorylation, enhanced medium. CONCLUSIONS These data support hypothesis that act upon stimulate signaling describe novel mechanism cross-talk between mediated part PTPRF. Prostate 73: 801–812, 2013. © 2012 Wiley Periodicals, Inc.