Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A |
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Authors: | Conejo-Garcia Jose R Benencia Fabian Courreges Maria-Cecilia Kang Eugene Mohamed-Hadley Alisha Buckanovich Ronald J Holtz David O Jenkins Ann Na Hana Zhang Lin Wagner Daniel S Katsaros Dionyssios Caroll Richard Coukos George |
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Institution: | Center for Research in Reproduction and Women's Health, University of Pennsylvania Medical Center, BRBII/III, 421 Curie Blvd, Philadelphia, Pennsylvania 19104, USA. |
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Abstract: | The involvement of immune mechanisms in tumor angiogenesis is unclear. Here we describe a new mechanism of tumor vasculogenesis mediated by dendritic cell (DC) precursors through the cooperation of beta-defensins and vascular endothelial growth factor-A (Vegf-A). Expression of mouse beta-defensin-29 recruited DC precursors to tumors and enhanced tumor vascularization and growth in the presence of increased Vegf-A expression. A new leukocyte population expressing DC and endothelial markers was uncovered in mouse and human ovarian carcinomas coexpressing Vegf-A and beta-defensins. Tumor-infiltrating DCs migrated to tumor vessels and independently assembled neovasculature in vivo. Bone marrow-derived DCs underwent endothelial-like differentiation ex vivo, migrated to blood vessels and promoted the growth of tumors expressing high levels of Vegf-A. We show that beta-defensins and Vegf-A cooperate to promote tumor vasculogenesis by carrying out distinct tasks: beta-defensins chemoattract DC precursors through CCR6, whereas Vegf-A primarily induces their endothelial-like specialization and migration to vessels, which is mediated by Vegf receptor-2. |
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