Neuroepithelial interactions in prostate cancer are enhanced in the presence ofprostatic stroma

Abstract

Objectives To develop an in vitro model that tests the involvement of prostatic stroma in the active reciprocal interactions between malignant epithelial cells and nerves that occur in perineural invasion. Methods Each of three metastatic prostate cancer cell lines (LnCaP, PC3, and DU-145 at 10 3) was co-cultured in sextuplet experiments with a human prostate stromal cell line (HTS-40C at 10 3) and a mouse dorsal root ganglion in matrigel for 13 days. Carcinoma/ganglia co-cultures (10 6 cells) in the absence of stroma served as controls. Areas of carcinoma cell growth (day 1), neurite growth (days 1 and 3), and perineural invasion (neuroepithelial halo area, day 11) were quantified. Results Mean neurite outgrowth was enhanced in the presence of stroma with LnCaP and PC3, but not with DU-145. Perineural invasion and carcinoma cell growth were enhanced in the presence of stroma in experiments with all three cell lines. The mean cell area (in square millimeters) increased 54.7% with LnCaP in the presence of stroma ( P <0.001). PC3 and DU-145 growth was enhanced 88.5% and 43.4%, respectively, in the presence of stroma. The mean neurite growth (in millimeters) on days 1 and 3 increased 50.8% and 70.8% with LnCaP in the presence of stroma. This enhancement was observed with PC3 by 88.1% and 64.5%. The mean neurite growth decreased in the presence of stroma with DU-145 by 4.9% and 5.4%. Perineural invasion increased 33.8% in the presence of stroma with LnCaP and 24.3% and 26.1% with PC3 and DU-145, respectively. Conclusions These novel findings strongly suggest active stromal participation in perineural invasion. The identification of specific stromal factors may suggest ways of preventing the progression of prostate cancer.