Abstract 3118: Regulation of SDF-1 (CXCL12) production by mesenchymal stromal cells

Abstract

Abstract The tumor microenvironment is made up of a number of cell types including neoplastic epithelial cells, myofibroblasts, smooth muscle cells, pericytes, adipocytes, endothelial cells and their precursors, fibroblasts and immune cells. The interaction between cellular components of the microenvironment is critical for processes such as tumor progression, growth, angiogenesis, and metastasis. Mesenchymal stromal cells (MSCs) are an important component of the tumor microenvironment with roles in key aspects of tumor development 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 an important regulator of SDF-1 signaling in MSCs within the tumor stroma. A decrease in p53 function leads to increased SDF-1 production by MSCs and increased migration of MSCs in response to tumor cells. An improved understanding of the molecular mechanisms controlling SDF-1 production by MSCs may identify novel ways to therapeutically target tumor – stromal interactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3118. doi:10.1158/1538-7445.AM2011-3118