Abstract 5160: Tumor cells potentiate mesenchymal stem cells-pericytes transition and requirement through PDGF-BB-NRP-1 axis

Abstract

Abstract New blood vessel formation or angiogenic switch is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells is unknown. In this study we focus on the role of tumor cells in governing the differentiation of mesenchymal stem cells (MSCs) to pericytes and their recruitment in tumor angiogenesis process. We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cells-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro condition. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, the invasive cells recruit less pericytes as compared to non-invasive cells. We identify tumor cell-secreted platelet derived growth factor (PDGF-BB) as a crucial factor controlling differentiation and recruitment processes through a cross-talk with NRP-1. These new insights into the roles of tumor cell-secreted PDGF in MSCs-fate determination may help in developing new antiangiogenic strategies to prevent the tumor growth and metastasis and also to treat cancers more effectively. 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 5160.