title: Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways.
abstract: Endothelial cell growth and proliferation are critical for angiogenesis; thus, greater insight into the regulation of pathological angiogenesis is greatly needed. Previous studies have reported on chemokine (C-X-C motif) ligand 1 (CXCL1) expression in epithelial cells and that secretion of CXCL1 from these epithelial cells induces angiogenesis. However, limited reports have demonstrated CXCL1 expression in endothelial cells. In this report, we present data that expand on the role of CXCL1 in human endothelial cells inducing angiogenesis. Specifically, CXCL1 is expressed and secreted from human endothelial cells. Interference of CXCL1 function using neutralizing antibodies resulted in a reduction in endothelial cell migration and viability/proliferation, the latter associated with a decrease in levels of cyclin D and cdk4. In vitro studies revealed that CXCL1 influenced neoangiogenesis through the regulation of epidermal growth factor and ERK1/2. In a xenograft angiogenesis model, interference of CXCL1 function resulted in inhibition of angiogenesis. A better understanding of the role of CXCL1 in the interactions between the endothelial and epithelial components will provide insight into how human tissues use CXCL1 to survive and thrive in a hostile environment.
authors.affiliation: Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, FL, USA.
authors.forename: Makito
authors.initials: M
authors.lastname: Miyake
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
authors.forename: Virginia
authors.initials: V
authors.lastname: Urquidi
authors.forename: Evan
authors.initials: E
authors.lastname: Gomes Giacoia
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D002465:Cell Movement; D054360:Chemokine CXCL1 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D023063:Receptors, Interleukin-8B / Q000378:metabolism
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D023063:Receptors, Interleukin-8B; D004815:Epidermal Growth Factor