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Calcium signaling in prostate cancer cells: Evidence for multiple receptors and enhanced sensitivity to bombesin/GRP

1997; Wiley; Volume: 30; Issue: 3 Linguagem: Inglês

10.1002/(sici)1097-0045(19970215)30

1097-0045

William J. Wasilenko, J. R. Cooper, Ann J. Palad, Kenneth D. Somers, P F Blackmore, Johng S. Rhim, George L. Wright, Paul F. Schellhammer,

Ion Channels and Receptors

BACKGROUND Cellular calcium is an important second messenger for growth regulation. We sought to identify potentially important receptors on prostate tumor cells by screening over 20 agonists for their ability to increase intracellular free calcium ([Ca2+]i) in several human prostate tumor cell lines. METHODS Intracellular calcium mobilization was detected using fura-2. RESULTS We found bombesin, GRP, ATP/UTP, lysophosphatidic 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 prostate cell line. Rank-order of potency studies suggested the presence of P2U nucleotide receptors for ATP/UTP on prostate epithelial cells. Potency studies also revealed GRP>>bombesin>>neuromedin B at elevating [Ca2+]i in responding tumor cells. CONCLUSIONS These findings indicate that androgen independent prostate tumor cell lines express multiple receptors capable of elevating intracellular calcium, and suggest that GRP receptors may be selectively expressed and/or coupled to calcium signaling during prostate tumor progression. Calcium sensitive cellular events may therefore contribute to the progression of prostate cancer. Prostate 30:167–173, 1997. © 1997 Wiley-Liss, Inc.