Abstract 1489: Exosomes are key players in nicotine-induced angiogenesis

Abstract

Abstract Nicotine, an addictive component of cigarette smoke and tobacco, have been shown to promote cancer pathogenesis. Angiogenesis is an important hallmark of cancer that sustains the supply of nutrients and oxygen to the fast proliferating cancer cells through the formation of new blood vessels. The goal of present study was to examine the direct and indirect effect of nicotine on endothelial cell growth, their migration and invasion, and capillary forming ability. We treated the human umbilical vein endothelial cells with two doses of nicotine within physiological range of smokers (200nM and 400nM) and examined the effect on their growth. In parallel, we treated the prostate cancer cells with similar doses of nicotine or vehicle for 8 h and subsequently replaced the media. After next 48 h, conditioned media (CM) was collected from vehicle- (Veh-CM) and nicotine- (Nic-CM) treated prostate cancer cells and used for the treatment of endothelial cells. The growth of endothelial cells increased by ~19 % and ~22 % upon direct treatment of nicotine at 200nM and 400nM doses, respectively. However, a far greater increase was recorded (~128% and ~ 146%, respectively), when endothelial cells were treated with the conditioned media derived from nicotine-treated cancer cells at 200nM and 400nM doses. In next of experiments, we fractionated Veh-CM and Nic-CM (200nM dose) into soluble and exosomal fractions and examined their effect on endothelial cells. We observed that exosomal fraction was more potent (~89%) in inducing endothelial cell growth as compared to the soluble fraction (~46%). In addition, we also observed significant greater increase in motility, invasion and capillary-forming ability of endothelial cells that were pre-treated with Nic-Exo as compared to those treated with Veh-Exo. Studies are currently ongoing to examine the comparative efficacy of nicotine-treated soluble and exosomal factions in potentiating motility, invasion and capillary formation and define the underlying molecular mechanism(s). Our findings thus support a novel pathogenic role of nicotine in cancer where exosomes act as key players in promoting angiogenesis. Citation Format: Shubhangi Singh, Sirin Saranyutanon, Mohammad Aslam Khan, Sanjeev Kumar Srivastava, Seema Singh, Ajay P. Singh. Exosomes are key players in nicotine-induced angiogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1489.