Distinct Roles of Vascular Endothelial Growth Factor-D in Lymphangiogenesis and Metastasis
| Autor: | Lucie Kopfstein, Karin Strittmatter, Marc G. Achen, Gerhard Christofori, Tanja Veikkola, Vanessa Baeriswyl, Tibor Schomber, Steven A. Stacker, Kari Alitalo, Valentin Djonov |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Pathology medicine.medical_specialty Lung Neoplasms Genotype Recombinant Fusion Proteins Immunoblotting Vascular Endothelial Growth Factor D Mice Transgenic Biology Pathology and Forensic Medicine Metastasis chemistry.chemical_compound Mice Microscopy Electron Transmission medicine Leukocytes Animals Humans Lymph sacs Lymphangiogenesis Neoplasm Metastasis Lymph node Cells Cultured Lymphatic Vessels Neovascularization Pathologic medicine.disease Rats Vascular endothelial growth factor Mice Inbred C57BL Pancreatic Neoplasms medicine.anatomical_structure Lymphatic system chemistry Vascular endothelial growth factor C Microscopy Electron Scanning Female Lymph Nodes Regular Articles |
| Popis: | In many human carcinomas, expression of the lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D) correlates with up-regulated lymphangiogenesis and regional lymph node metastasis. Here, we have used the Rip1Tag2 transgenic mouse model of pancreatic beta-cell carcinogenesis to investigate the functional role of VEGF-D in the induction of lymphangiogenesis and tumor progression. Expression of VEGF-D in beta cells of single-transgenic Rip1VEGF-D mice resulted in the formation of peri-insular lymphatic lacunae, often containing leukocyte accumulations and blood hemorrhages. When these mice were crossed to Rip1Tag2 mice, VEGF-D-expressing tumors also exhibited peritumoral lymphangiogenesis with lymphocyte accumulations and hemorrhages, and they frequently developed lymph node and lung metastases. Notably, tumor outgrowth and blood microvessel density were significantly reduced in VEGF-D-expressing tumors. Our results demonstrate that VEGF-D induces lymphangiogenesis, promotes metastasis to lymph nodes and lungs, and yet represses hemangiogenesis and tumor outgrowth. Because a comparable transgenic expression of vascular endothelial growth factor-C (VEGF-C) in Rip1Tag2 has been shown previously to provoke lymphangiogenesis and lymph node metastasis in the absence of any distant metastasis, leukocyte infiltration, or angiogenesis-suppressing effects, these results reveal further functional differences between VEGF-D and VEGF-C. |
| Databáze: | OpenAIRE |
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