CALCIUM SIGNALING IN PROSTATE-CANCER CELLS - EVIDENCE FOR MULTIPLE RECEPTORS AND ENHANCED SENSITIVITY TO BOMBESIN GRP/

BACKGROUND. Cellular calcium is an important second messenger for grow th regulation. We sought to identify potentially important receptors o n prostate tumor cells by screening over 20 agonists for their ability to increase intracellular free calcium ([Ca2+](i)) in several human p rostate tumor cell lines. METHODS. Intracellular calcium mobilization was detected using fura-2. RESULTS. We found bombesin, GRP, ATP/UTP, l ysophosphatidic acid, thrombin, endothelin, histamine, and bradykinin increased [Ca2+](i) in the advanced tumor cell lines DU-145, PC3, and PPC-1. Bombesin failed to elevate [Ca2+](i) in an immortalized human p rostate cell line. Rank-order of potency studies suggested the presenc e of P-2U nucleotide receptors for ATP/UTP on prostate epithelial cell s. Potency studies also revealed GRP>>bombesin>>neuromedin B at elevat ing [Ca2+](i) in responding tumor cells. CONCLUSIONS. These findings i ndicate that androgen independent prostate tumor cell lines express mu ltiple receptors capable of elevating intracellular calcium, and sugge st that GRP receptors may be selectively expressed and/or coupled to c alcium signaling during prostate tumor progression. Calcium sensitive cellular events may therefore contribute to the progression of prostat e cancer. (C) 1997 Wiley-Liss, Inc.