Blocking SDF-1α/CXCR4 downregulates PDGF-B and inhibits bone marrow-derived pericyte differentiation and tumor vascular expansion in Ewing tumors.

ABSTRACT: Bone marrow cells (BMC) are critical to the expansion of the tumor vessel network that supports Ewing sarcoma growth. BMCs migrate to the tumor and differentiate into endothelial cells and pericytes. We recently demonstrated that stromal-derived growth factor 1α (SDF-1α) regulates platelet-derived growth factor B (PDGF-B) and that this pathway plays a critical role in bone marrow-derived pericyte differentiation in vitro. We investigated the role of SDF-1α/PDGF-B in the tumor microenvironment in vivo in promoting bone marrow-derived pericyte differentiation in Ewing tumors. The CXCR4 antagonist AMD 3100 was used to disrupt the SDF-1α/CXCR4 axis in vivo in two xenograft Ewing tumor models. BMCs from GFP(+) transgenic mice were transplanted into lethally irradiated nude mice to track BMC mig

SUBMITTER: Hamdan R 

PROVIDER: S-EPMC3926209 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature