Abstract 1060: Regulation of SDF-1 (CXCL12) production by mesenchymal stromal cells in the tumor microenvironment

Abstract

Abstract The tumor microenvironment is made up of a number of cell types including fibroblasts, pericytes, endothelial cells, macrophages, and neoplastic cells. The interaction between cellular components of the microenvironment is critical for processes such as tumor growth, angiogenesis, and metastasis. Mesenchymal stromal cells (MSCs) are an important component of the tumor microenvironment with roles in key aspects of tumor progression such as cell growth and metastasis. Stromal-derived factor −1 (SDF-1) has been identified as a key signaling molecule in the interaction between MSCs and neoplastic cells. SDF-1 acting through its cognate receptors CXCR4 and CXCR7 is known to mediate diverse processes such as chemotaxis, angiogenesis, hematopoiesis, metastasis, and tumor growth. In this study we investigated the regulation of SDF-1 production by MSCs. We show that the tumor suppressor p53 is one of the major regulators of SDF-1 signaling in MSCs within the tumor stroma. We also illustrate that a decrease in p53 function leads to increased SDF-1 production by MSCs which results in increased migration of MSCs. Decreased p53 expression by MSCs leads to increased SDF-1 production with and increased recruitment to the tumor microenvironment. An improved understanding of the molecular mechanisms controlling SDF-1 production by MSCs may identify novel ways of therapeutically targeting tumor - stromal interactions. 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 1060.