Data from Vascular Adhesion Protein-1 Enhances Tumor Growth by Supporting Recruitment of Gr-1<sup>+</sup>CD11b<sup>+</sup> Myeloid Cells into Tumors

Abstract

<div>Abstract<p>Cancer growth is regulated by several nonmalignant cell types, such as leukocytes and endothelial cells, which reside in the stroma of the tumor. Vascular adhesion protein-1 (VAP-1) is an amine oxidase enzyme that is expressed on the surface of endothelial cells. It supports leukocyte traffic into inflamed tissues, but nothing is known about its possible role in cancer biology <i>in vivo</i>. Here, we report that B16 melanoma and EL-4 lymphoma remain smaller in VAP-1–deficient mice than in wild-type controls. We found an unexpected defect in tumor angiogenesis in the absence of VAP-1. VAP-1 also selectively enhanced the recruitment of Gr-1<sup>+</sup>CD11b<sup>+</sup> myeloid cells into the tumors. Generation of mice expressing enzymatically inactive VAP-1 showed that the oxidase activity of VAP-1 was necessary to support neoangiogenesis, myeloid cell recruitment, and tumor growth <i>in vivo</i>. These data describe VAP-1 as the first adhesion molecule known to be involved in the recruitment of Gr-1<sup>+</sup>CD11b<sup>+</sup> myeloid cells into tumors. They also suggest that VAP-1 is a potential new tool for immunotherapy of tumors that could be exploited to reduce tumor burden by controlling the traffic of Gr-1<sup>+</sup>CD11b<sup>+</sup> myeloid cells. [Cancer Res 2009;69(19):7875–83]</p></div>