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Endothelial CXCL12 regulates neovascularization during tissue repair and tumor progression

ABSTRACT: Tissue repair and tumor progression are linked by their reliance on the response to ischemia. Coordinated interplay between resident and circulating cells, governed by a myriad of factors, is critical for new blood vessel formation and tissue survival in both. The vascular endothelium exhibits paracrine activity and provides an interface for the recruitment of circulating cells, which in turn influence the neovascularization and extra-vascular tissue growth. CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1 [SDF-1]) has been implicated in tumor biology and neovascularization, but its specific role and mechanism of action remain poorly understood. We have previously demonstrated that CXCL12 expression is hypoxia responsive and occurs in vascular endothelium. Here we use a conditional CXCL12 knockout mouse to show that endothelial-specific deletion of CXCL12 (eKO) reduces the survival of ischemic tissue, which alters both tissue repair and tumor progression. The loss of vascular endothelial CXCL12 disrupts endothelial – fibroblast crosstalk necessary for stromal growth and vascularization. Using single-cell gene expression analysis in combination with a parabiosis model, eKO is found to impair the recruitment of a specific population of non-inflammatory circulating cells defined by genes regulating cell survival and neovascularization. These findings indicate an essential role of endothelial CXCL12 expression during the adult neovascular response in tissue injury and tumor progression, paving the way for future therapeutic interventions.

ORGANISM(S): Mus musculus

PROVIDER: GSE146529 | GEO | 2020/03/07

REPOSITORIES: GEO

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Endothelial CXCL12 regulates neovascularization during tissue repair and tumor progression

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