Abstract A74: Microparticles mediate cross-talk between tumoral and endothelial cells and promote the constitution of an angiocrine pro-metastatic niche through Arf6 up regulation

Abstract

During the past few years, evidences in the literature point out the crucial role of the microenvironment in tumor growth, resistance to therapy and occurrence of metastatic phenotype. Tumor vessels have been considered for a long time as passive conducts for nutriments but more recently several studies have also demonstrated secretion of pro-tumoral factors by endothelial cells. It seems therefore mandatory to clearly identify the mechanisms mediating cross-talk between tumor cells and endothelial cells. Here, we hypothetize that tumor cell and endothelium secrete bio-active microparticles (MPs) that are actively uptaken by the other cell type and that are participating to a functional cross-talk. We characterized the cancer cells MPs, using 2 cells lines from breast cancer (MCF7, MDA-MB231) and 2 from ovarian cancer (SKOV3, OVCAR3) and the endothelium secreted MPs using E4orf1-activated endothelium. Our data show that MPs from mesenchymal-like metastatic cell lines (MDA-MB231 and SKOV3) were able to promote an angiocrine switch of endothelial cells (activation of akt signaling) compared to MPs from epithelial-like cell lines (OVCAR3 and MCF7). The angiocrine switch increased Arf6 expression and functionalized an MP dependent vascular niche enhancing tumor cells pro-metastatic proprieties. We also show that angiocrine endothelial MPs enhanced tumor cells pro-metastatic proprieties and cancer stemness. All together we demonstrated that cancer cell derived MPs induced or sustain both an angiogenic but also an angiocrine switch of the endothelium. This has great implication in terms of tumor biology as indeed while the emphasis has mainly been on the angiogenic properties, the angiocrine pro-tumoral effect might be the cause for therapeutic resistance as well as residual and recurrent disease. Citation Format: Jennifer Pasquier, Hamda Al. Thawadi, Nadine Abu Kaoud, Pegah Ghiabi, Mahtab Maleki, Bella S. Guerrouahen, Arash Rafii. Microparticles mediate cross-talk between tumoral and endothelial cells and promote the constitution of an angiocrine pro-metastatic niche through Arf6 up regulation. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A74.