The angiogenic response is dictated by beta3 integrin on bone marrow-derived cells.
Angiogenesis is dependent on the coordinated action of numerous cell types. A key adhesion molecule expressed by these cells is the alpha(v)beta(3) integrin. Here, we show that although this receptor is present on most vascular and blood cells, the key regulatory function in tumor and wound angiogenesis is performed by beta(3) integrin on bone marrow-derived cells (BMDCs) recruited to sites of neovascularization. Using knockin mice expressing functionally stunted beta(3) integrin, we show that bone marrow transplantation rescues impaired angiogenesis in these mice by normalizing BMDC recruitment. We demonstrate that alpha(v)beta(3) integrin enhances BMDC recruitment and retention at angiogenic sites by mediating cellular adhesion and transmigration of BMDCs through the endothelial monolayer but not their release from the bone niche. Thus, beta(3) integrin has the potential to control processes such as tumor growth and wound healing by regulating BMDC recruitment to sites undergoing pathological and adaptive angiogenesis.
Feng
Weiyi
W
Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
McCabe
N Patrick
NP
Mahabeleshwar
Ganapati H
GH
Somanath
Payaningal R
PR
Phillips
David R
DR
Byzova
Tatiana V
TV
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D055879:Gene Knock-In Techniques; D006410:Hematopoiesis; D039661:Integrin beta3 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism; D014945:Wound Healing
D054377:Chemokine CXCL12; D039661:Integrin beta3; D019718:Receptors, CXCR4