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Published online
doi:10.1083/jcb.200802179
The Journal of Cell Biology, Vol. 183, No. 6, 1145-1157
The Rockefeller University Press, 0021-9525 $30.00
© Feng et al.
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Article

The angiogenic response is dictated by β3 integrin on bone marrow–derived cells



Weiyi Feng1, N. Patrick McCabe1, Ganapati H. Mahabeleshwar1, Payaningal R. Somanath1, David R. Phillips2, and Tatiana V. Byzova1

1 Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195
2 Portola Pharmaceuticals Incorporated, South San Francisco, CA 94080

Correspondence to Tatiana V. Byzova: byzovat{at}ccf.org

Angiogenesis is dependent on the coordinated action of numerous cell types. A key adhesion molecule expressed by these cells is the {alpha}vβ3 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 β3 integrin on bone marrow–derived cells (BMDCs) recruited to sites of neovascularization. Using knockin mice expressing functionally stunted β3 integrin, we show that bone marrow transplantation rescues impaired angiogenesis in these mice by normalizing BMDC recruitment. We demonstrate that {alpha}vβ3 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, β3 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.

W. Feng's present address is The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Abbreviations used in this paper: BM, bone marrow; BMDC, BM-derived cell; BMT, BM transplantation; NG2, neuro/glial cell 2 chondroitin proteoglycan; SDF-1, stromal derived factor-1; SMA, smooth muscle actin; TRAcP, tartrate-resistant acid phosphatase; VE, vascular endothelium; WT, wild type.

© 2008 Feng et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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