Data from SDF-1α Induces PDGF-B Expression and the Differentiation of Bone Marrow Cells into Pericytes

Abstract

<div>Abstract<p>Platelet-derived growth factor B (PDGF-B) and its receptor, PDGFR-β, play a critical role in pericyte maturation; however, the mechanisms by which PDGF-B is upregulated in the tumor microenvironment remain unclear. We previously showed that upregulating stromal-derived factor, SDF-1α, in VEGF<sub>165</sub>-inhibited Ewing's sarcoma tumors (TC/siVEGF<sub>7-1</sub>) induced PDGF-B mRNA expression, increased infiltration and differentiation of bone marrow cells (BMC) into pericytes and, rescued tumor growth. The purpose of this study was to investigate the mechanism by which SDF-1α increased PDGF-B expression and the role of this pathway in BM-derived pericyte differentiation. We showed that SDF-1α induced expression of PDGF-B mRNA and protein both <i>in vitro</i> and <i>in vivo</i>. In contrast, inhibiting SDF-1α downregulated PDGF-B. We cloned the 2-kb <i>pdgf-b</i> promoter fragment and showed that SDF-1α activates PDGF-B via a transcriptional mechanism. Chromatin immunoprecipitation showed that the ELK-1 transcription factor binds to the <i>pdgf-b</i> promoter in response to SDF-1α. We confirmed the correlation between the SDF-1α/PDGF-B pathway and the differentiation of PDGFR-β+ BMCs into mature pericytes using an <i>in vitro</i> assay. These findings show that SDF-1α regulates PDGF-B expression and that this regulation plays a critical role in the differentiation of PDGFR-β+ BMCs into mature pericytes. <i>Mol Cancer Res; 9(11); 1462–70. ©2011 AACR</i>.</p></div>