Nature Medicine10, 950 - 958 (2004)
Published online: 29 August 2004; | doi:10.1038/nm1097
Tumor-infiltrating dendritic cell precursors recruited by a -defensin contribute to vasculogenesis under the influence of Vegf-A
Jose R Conejo-Garcia1, 5, Fabian Benencia1, 5, Maria-Cecilia Courreges1, Eugene Kang1, Alisha Mohamed-Hadley1, Ronald J Buckanovich1, David O Holtz1, Ann Jenkins1, Hana Na1, Lin Zhang1, 2, Daniel S Wagner3, Dionyssios Katsaros4, Richard Caroll2
& George Coukos1, 2
1
Center for Research in Reproduction and Women's Health, University of Pennsylvania Medical Center, BRBII/III, 421 Curie Blvd, Philadelphia, Pennsylvania 19104, USA.
2
Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, BRBII/III, 421 Curie Blvd, Philadelphia, Pennsylvania 19104, USA.
3
Department of Cell and Developmental Biology, University of Pennsylvania Medical Center, BRBII/III, 421 Curie Blvd, Philadelphia, Pennsylvania 19104, USA.
4
Department of Obstetrics and Gynecology, University of Turin, 10126 Turin, Italy.
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 -defensins and vascular endothelial growth factor-A (Vegf-A). Expression of mouse -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 -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 -defensins and Vegf-A cooperate to promote tumor vasculogenesis by carrying out distinct tasks: -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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-defensin contribute to vasculogenesis under the influence of Vegf-A
-defensins and vascular endothelial growth factor-A (Vegf-A). Expression of mouse 
