Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of Vegf-A
| Autor: | Eugene Kang, Dionyssios Katsaros, Jose R. Conejo-Garcia, George Coukos, Fabian Benencia, Ronald J. Buckanovich, Maria C. Courreges, Daniel S. Wagner, Alisha Mohamed-Hadley, Richard Caroll, Ann Jenkins, Hana Na, Lin Zhang, David O. Holtz |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Vascular Endothelial Growth Factor A
Pathology medicine.medical_specialty beta-Defensins VEGF receptors Immunoblotting Population C-C chemokine receptor type 6 General Biochemistry Genetics and Molecular Biology Mice Vasculogenesis Cell Movement In vivo medicine Animals education Defensin education.field_of_study Neovascularization Pathologic biology Histological Techniques Cell Differentiation hemic and immune systems Dendritic Cells General Medicine Dendritic cell Flow Cytometry Drug Combinations biology.protein Cancer research Angiogenesis Inducing Agents Proteoglycans Receptors Chemokine Collagen Laminin Ex vivo |
| Zdroj: | Nature Medicine. 10:950-958 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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