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 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.
Wasilenko
W J
WJ
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23510, USA.
Cooper
J
J
Palad
A J
AJ
Somers
K D
KD
Blackmore
P F
PF
Rhim
J S
JS
Wright
G L
GL
Schellhammer
P F
PF
D001839:Bombesin / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D009479:Neuropeptides; D018004:Receptors, Bombesin; D001839:Bombesin; D002118:Calcium