Abstract 2485: Heterozygous deletion of RUNX3 promotes vasculogenesis by enhancing endothelial progenitor cells function

Abstract

Abstract Endothelial progenitor cells (EPCs) are bone marrow (BM) -derived stem cells to be committed and differentiated into mature endothelial cells. Runt-related transcription factor 3 (RUNX3) is a tumor suppressor involved in TGF-β signaling pathway and participate in cell cycle arrest and anti-angiogenesis. RUNX3 is frequently deleted or transcriptionally silenced in a variety of cancers by epigenetic mechanisms. The aim of study was to determine the role of RUNX3 in EPC function and vasculogenesis. Here we found that RUNX3 homozygous knockout (Rx3-/-) embryos had vascular defects in embryonic day (ED) 10 and developmental abnormalities in ED 16.5 organs. The number of EPC colonies and circulating EPCs (CD34+/VEGFR2+ cells), migration and tube formation capacity of EPCs derived from RUNX3 heterozygous (Rx3+/-) mice were increased in compared to those wild type (WT) mice, suggesting that deletion of RUNX3 can enhance vasculogenesis. Expression level of VEGF, VEGFR2, SDF-1, CXCR4 and endothelial nitric oxide synthase (eNOS) mRNA was significantly up-regulated in Rx3+/- EPCs. Protein expression of VEGF, p-VEGFR2, p-Akt, p-ERK, p-SAPK/JNK and p-eNOS was also augmented in Rx3+/- EPCs. Finally, we found that recovery of blood flow was highly stimulated in Rx3+/- mice using hindlimb ischemia mouse models. Taken together, our study revealed that RUNX3 might inhibit vasculogenic processes in physiological ischemia by inhibition of EPC functions. Citation Format: Su Young Oh, Se-Hyung Lee, Sun Hee Lee, You Mie Lee. Heterozygous deletion of RUNX3 promotes vasculogenesis by enhancing endothelial progenitor cells function. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2485.