Hepatocyte growth factor supports androgen stimulation of growth of mouse ventral prostate epithelial cells in collagen gel matrix culture

To assess the role of hepatocyte growth factor (HGF) and androgen in growth of prostate epithelial cells, we isolated mouse ventral prostate epithelial cells and cultured them in a three-dimensional type I collagen gel matrix under serum-free conditions. Although the prostate epithelial cells tended to die in the insulin-supplemented basal medium, 5alpha-dihydrotestosterone (DHT) prevented the cell death, and HGF slightly stimulated the growth. By contrast, coexistence of DHT and HGF greatly augmented the growth and branching morphogenesis of the epithelial cells. Some of the outgrowths formed under these conditions showed enlarged structures resembling the prostate ducts or alveoli. Examination of the stromal cell-conditioned medium revealed that a growth-stimulating activity is present in the conditioned medium. A major portion of this activity was abolished by anti-HGF IgG. These observations suggest that HGF is produced by the stromal cells of the prostate gland and supports the androgen stimulation of growth of the epithelial cells.