Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A

Nat Med. 2004 Sep;10(9):950-8. doi: 10.1038/nm1097. Epub 2004 Aug 29.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inducing Agents / immunology*
  • Animals
  • Cell Differentiation / immunology
  • Cell Movement / immunology
  • Collagen
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Drug Combinations
  • Flow Cytometry
  • Histological Techniques
  • Immunoblotting
  • Laminin
  • Mice
  • Neovascularization, Pathologic / immunology*
  • Proteoglycans
  • Receptors, Chemokine / metabolism
  • Vascular Endothelial Growth Factor A / metabolism*
  • beta-Defensins / immunology*
  • beta-Defensins / metabolism


  • Angiogenesis Inducing Agents
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • Receptors, Chemokine
  • Vascular Endothelial Growth Factor A
  • beta-Defensins
  • vascular endothelial growth factor A, mouse
  • matrigel
  • Collagen