Angiogenesis is not mediated by prostate cancer neuropeptides.
Once metastatic, prostate cancer (CaP) treatment options are limited to androgen withdrawal. In this environment, the cells often develop an androgen independent state resulting in patient demise. It has been shown that during this transition, CaP cells transdifferentiate to neuroendocrine cells, which produce neuropeptides. These neuropeptides have a mitogenic effect on surrounding CaP cells. Previous observations suggest that endothelial cells may show a similar mitogenic response to neuropeptides, implicating angiogenesis in the progression of CaP. We stimulated human umbilical endothelial cells (HUVECs) with the neuropeptides bombesin and neurotensin and measured proliferation, migration, cell tube formation, and tyrosine kinase activation. In our studies, neurotensin and bombesin did not stimulate HUVEC proliferation, migration, nor tube formation. Although HUVECs express the non-receptor tyrosine kinases Fak, Src, and Etk which mediate neuropeptide signaling in CaP, they are not activated by neuropeptides in HUVECs.
Busby
J E
JE
Department of Urology, University of California, Davis, School of Medicine, Sacramento, California 95817, USA.
Shih
S-J
SJ
Yang
J C
JC
Kung
H-J
HJ
Evans
C P
CP
D015153:Blotting, Western; D001839:Bombesin / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology; D011233:Precipitin Tests; D011471:Prostatic Neoplasms / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D019061:src-Family Kinases / Q000378:metabolism
D009479:Neuropeptides; D042461:Vascular Endothelial Growth Factor A; D009496:Neurotensin; C492367:BMX protein, human; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019061:src-Family Kinases; D001839:Bombesin