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Integrin ₄ß₁ Promotes Monocyte Trafficking and Angiogenesis in Tumors

¹ John and Rebecca Moores Comprehensive Cancer Center and ² Department of Medicine, University of California at San Diego, San Diego, California

Requests for reprints: Judy Varner, John and Rebecca Moores Comprehensive Cancer Center, University of California at San Diego, 3855 Health Sciences Drive #0819, La Jolla, CA 92093-0819. Phone: 858-822-0086; Fax: 858-822-1325; E-mail: jvarner{at}ucsd.edu.

Monocytes and macrophages extensively colonize solid tumors, where they are thought to promote tumor angiogenesis. Here, we show that integrin ₄ß₁ (VLA4) promotes the invasion of tumors by myeloid cells and subsequent neovascularization. Antagonists of integrin ₄ß₁, but not of other integrins, blocked the adhesion of monocytes to endothelium in vitro and in vivo as well as their extravasation into tumor tissue. These antagonists prevented monocyte stimulation of angiogenesis in vivo, macrophage colonization of tumors, and tumor angiogenesis. These studies indicate the usefulness of antagonists of integrin ₄ß₁ in suppressing macrophage colonization of tumors and subsequent tumor angiogenesis. These studies further indicate that suppression of myeloid cell homing to tumors could be a useful supplementary approach to suppress tumor angiogenesis and growth. (Cancer Res 2006; 66(4):2146-52)

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