Endothelial-monocyte activating polypeptide II alters fibronectin based endothelial cell adhesion and matrix assembly via alpha5 beta1 integrin.
Mature Endothelial-Monocyte Activating Polypeptide (mEMAP) II functions as a potent antiangiogenic peptide. Although the anti-tumor effect of mEMAP II has been described, little is known regarding its mechanism of action. Observations that mEMAP II induced apoptosis only in a subset of migrating and proliferating endothelial cells (EC) suggests a targeted effect on cells engaged in angiogenic activities which are known to rely upon cell adhesion and migration. Indeed, we demonstrate that mEMAP II inhibited fibronectin (FN) dependent microvascular EC (MEC) adhesion and spreading and we show that this depends upon the alpha5 beta1 integrin. Immunofluorescence analysis demonstrated that mEMAP II-dependent blockade of FN-alpha5 beta1 interactions was associated with disassembly of both actin stress fiber networks and FN matrix. These findings suggest that mEMAP II blocks MEC adhesion and spreading on fibronectin, via a direct interaction with the integrin alpha5 beta1, thus implicating that alpha5 integrin may be a mediator of mEMAP II's antiangiogenic function.
Schwarz
Margaret A
MA
Department of Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 125 Paterson Street, CAB 7319, New Brunswick, NJ 08903, USA. m.schwarz@umdnj.edu
Zheng
Hiahua
H
Liu
Jie
J
Corbett
Siobhan
S
Schwarz
Roderich E
RE
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects; D005353:Fibronectins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology*; D022502:Stress Fibers / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D005353:Fibronectins; D039081:Integrin alpha5beta1; D009363:Neoplasm Proteins; D009842:Oligopeptides; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; C047981:arginyl-glycyl-aspartic acid