Integrin alpha4beta1 promotes monocyte trafficking and angiogenesis in tumors.
Monocytes and macrophages extensively colonize solid tumors, where they are thought to promote tumor angiogenesis. Here, we show that integrin alpha4beta1 (VLA4) promotes the invasion of tumors by myeloid cells and subsequent neovascularization. Antagonists of integrin alpha4beta1, 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 alpha4beta1 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.
John and Rebecca Moores Comprehensive Cancer Center, University of California at San Diego, San Diego, California, USA.
Hui
H
Jin
Jingmei
J
Su
Barbara
B
Garmy-Susini
Jeanine
J
Kleeman
Judy
J
Varner
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D039041:Integrin alpha4beta1 / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology*; D042583:Lymphangiogenesis; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D022423:Myeloid Cells / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology
D039041:Integrin alpha4beta1