Abstract 783: Cancer cell-derived extracellular vesicles stimulate tumor angiogenesis by delivering VEGF to endothelial cells

Abstract

Abstract Angiogenesis is essential for tumor growth and metastasis, and is orchestrated by a repertoire of growth factor signaling pathways that stimulate endothelial cell growth, migration and vessel formation. Recent studies have shown that angiogenesis can also be regulated by cell-derived extracellular vesicles. Exosomes are small endosomal-derived membrane vesicles that contain various biomolecules such as RNA and proteins, and are increasingly thought to play important roles in transferring informational cargo between cancer cells and stromal cells. In the majority of studies to date, the effects of cancer cell-derived exosomes have been attributed to their RNA cargo. In this study, we identified that exosomes derived from ovarian, colon and renal cancer cells contain abundant vascular endothelial growth factor (VEGF). Cancer cell-derived exosomes were found to activate the VEGF signaling pathway in endothelial cells and to stimulate endothelial cell migration and tube formation. Furthermore, our studies using inhibitors of VEGF signaling demonstrated that the stimulatory effects of cancer cell-derived exosomes on endothelial cells depend on the presence of VEGF in exosomes and are mediated via the VEGF signaling pathway. These findings indicate that cancer cell-derived exosomes promote tumor angiogenesis by delivering VEGF to endothelial cells. Citation Format: Song Yi Ko, Honami Naora. Cancer cell-derived extracellular vesicles stimulate tumor angiogenesis by delivering VEGF to endothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 783. doi:10.1158/1538-7445.AM2017-783