Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells

We investigated the effect of various neuropeptides present in the prostate , including calcitonin gene-related peptide (CGRP), gastrin-releasing pepti de (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal pol ypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and p arathyroid hormone-related protein (PTH-rP), on the invasion of PC-3 prosta te cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the inv asive capacity of tumor cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon and PTH-rP had no significant effect. Both CG RP and GRP also increased the haptotactic migration of tumor cells to fibro nectin, but SP inhibited it. These three neuropeptides had no effect on eit her adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cel ls at concentrations used in this study. These results indicate that both G RP and CGRP increased the invasive potential of PC-3 cells probably through enhancement of cell motility, while SP inhibited the invasiveness through suppression of motile response. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.