Effect of heparan sulfate mimetics from Escherichia coli K5 polysaccharide on SDF-1/CXCL12-induced endothelial progenitor cells in vitro

Abstract

In tumorigenesis, CXCL12 level increases sharply because of tumor tissue hypoxia. As CXCR4 cells, endothelial progenitor cells (EPCs) are mobilized to tumor bed through the CXCL12/CXCR4 axis and are involved in tumor angiogenesis. In this process, either glycosaminoglycan (GAG) or heparan sulfate (HS) carried by membrane proteoglycans is implicated. Exogenous soluble HS mimetics can act as a competitive inhibitor of membranous HS, thereby preventing the formation of a normal signal axis. In this work, the effect of HS mimetics on the CXCL12-induced EPCs in vitro was investigated. HS mimetics, named as K5PSs, were obtained from sulfated Escherichia coli K5 polysaccharide/heparosan, and EPCs were collected from rat bone marrow. Results showed that CXCL12 could promote EPCs viability. This promotion might be related to its regulation of cell cycle and anti-apoptosis activity; it also could promote EPCs migration and secretion of pro-angiogenesis factors. All its functions were obtained by activation of MAPK/ERK pathway, FAK pathway, and PI3k/AKT pathway. However, its effect on EPCs was attenuated by K5PSs, and the existence of sulfate groups both at 2-O-position and N-position in K5PSs is essential to inhibit its effect on EPCs. This work suggested that K5PSs could be applied in anti-tumor treatment through inhibiting tumor angiogenesis.