VASOACTIVE-INTESTINAL-PEPTIDE STIMULATES PROSTATE-SPECIFIC ANTIGEN SECRETION BY LNCAP PROSTATE-CANCER CELLS

The secretion of prostate-specific antigen (PSA) by prostate cancer pr ovides an important tool in the diagnosis and management of this disor der. While androgens are required for PSA synthesis, the neuroendocrin e regulation of PSA secretion is less understood. Human prostate is ex tensively innervated with vasoactive intestinal peptide (VIP)-containi ng neurons, while both normal and malignant prostate cells contain VIP receptors. Therefore, we investigated the effects of VIP on PSA secre tion by LNCaP prostate cancer cells. We found that 1-4-h VIP treatment produces 60-100% increases in PSA secretion by LNCaP cells. Increases in PSA secretion were seen with as little as 10(-10) M VIP with maxim um effects at 10(-7) M. The predominant acute effect of VIP was to inc rease the secretion of stored PSA without increasing PSA mRNA. VIP's e ffect on PSA secretion involved the production of intracellular cAMP s ince all doses of VIP which increased secretion were associated with i ncreased cyclic AMP and since dibutyryl-cyclic AMP treatment increased secretion similarly to VIP. These results suggest that VIP regulates PSA secretion by prostate cancer cells and also suggest a role for VTP to regulate PSA secretion by normal prostate epithelial cells.