Abstract
Abstract Angiogenesis is a highly regulated biological complex process, which consist of endothelial cells proliferation, migration, and tubulogenesis as key cellular steps to form new blood capillaries from preexisting vessels. Imbalance in angiogenesis contributes to a variety of human diseases. Tumor growth depends on angiogenesis and antiangiogenic agents have been developed as effective anti-cancer medicine. Recently, we have demonstrated that serotonin (5-HT), a well-recognized neurotransmitter, has a promoting effect on endothelial cells proliferation, migration and tubulogenesis, suggesting serotonin plays a role in regulation of angiogenesis. To study the role of serotonin in angiogenesis, we examined the expression of serotonin receptor isoforms in human endothelial cells. Real time PCR studies have showed that, serotonin receptor 1B (HTR1B), 1D (HTR1D), 1A (HTR1A) and 2B (HTR2B) are expressed in primary human endothelial cell lines. Blocking serotonin 1B receptor had significant inhibitory effect on endothelial cells proliferation and tubulogenesis. We have further explored the 1B-mediated signal transduction in endothelial cells. The results have revealed that the serotonin 1B receptor as a G protein-coupled receptor (GPCR) is coupled to Gi protein and decreased intracellular cAMP level upon its receptor binding. Both serotonin and 1B receptor agonist were able to activate ERK, p38, Akt, RhoA, Rac1 and PYK2/FAK signaling in endothelial cells. In contrast, a selective antagonist for serotonin 1B receptor blocks the serotonin-stimulated Akt and PYK2/FAK activation. Experiments with pertussis toxin (general Gi blocker) further demonstrated that heterotrimeric Gi-protein is required for the activation of Akt and PYK2/FAK by serotonin. These findings suggest that Akt and PYK2/FAK are involved in signaling transduction in serotonin-activated endothelial cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2390.
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