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.