NEUROENDOCRINE PEPTIDES STIMULATE ADENYL-CYCLASE IN NORMAL AND MALIGNANT PROSTATE CELLS

Elevations of intracellular cAMP in human prostate cancer cells have b een shown to increase invasiveness and to promote neuronal differentia tion. Since neuroendocrine peptides capable of activating adenyl cycla se are present in prostatic nerves and epithelial neuroendocrine cells , we investigated normal and malignant human prostate cells for change s in intracellular cAMP in response to the prostatic peptides vasoacti ve intestinal peptide (VIP), calcitonin (CT), and calcitonin gene-rela ted peptide (CGRP). Normal prostate epithelial cells and LNCaP prostat e cancer cells exhibited, respectively, 6- and 30-fold increases in in tracellular cAMP in response to VIP. ALVA-31 and PPC-1 prostate cancer cells demonstrated 20- to 200-fold increases in cAMP in response to C GRP, while normal epithelial cells and LNCaP cells exhibited smaller ( 2- to 6-fold) responses. Only DU-145 cells increased cAMP substantiall y in response to CT. VIP receptor mRNA was identified by Northern blot analysis only in those cells that responded to VIP. CT receptor mRNA was identified only in DU-145 cells by polymerase chain reaction and S outhern blot analysis. These results suggest that VIP and possibly CGR P receptors are likely to be present in both normal and malignant pros tate cells. VIP or CGRP may regulate secretion of proteases by normal or prostate cancer cells and may influence epithelial cell differentia tion.