CXCL4L1–fibstatin cooperation inhibits tumor angiogenesis, lymphangiogenesis and metastasis
| Autor: | L. Van Den Berghe, Andreas Bikfalvi, Nadera Ainaoui, Hervé Prats, A. Rayssac, S. Legonidec, Françoise Pujol, Florent Morfoisse, Barbara Garmy-Susini, Anne-Catherine Prats, Stéphane Pyronnet |
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| Rok vydání: | 2013 |
| Předmět: |
Chemokine
DNA Complementary Angiogenesis Biology Platelet Factor 4 Biochemistry Metastasis Mice Cell Movement Neoplasms Human Umbilical Vein Endothelial Cells medicine Animals Humans Neoplasm Invasiveness Lymphangiogenesis Neoplasm Metastasis Cell Proliferation Neovascularization Pathologic Membrane Proteins Cell Biology medicine.disease Recombinant Proteins Endostatins Gene Expression Regulation Neoplastic Endothelial stem cell Drug Combinations Lymphatic system Tumor progression Immunology Disease Progression Cancer research biology.protein Proteoglycans Collagen Laminin Endostatin Carrier Proteins Cardiology and Cardiovascular Medicine Neoplasm Transplantation |
| Zdroj: | Microvascular Research. 89:25-33 |
| ISSN: | 0026-2862 |
| Popis: | Anti-angiogenic and anti-lymphangiogenic drugs slow tumor progression and dissemination. However, an important difficulty is that a tumor reacts and compensates to obtain the blood supply needed for tumor growth and lymphatic vessels to escape to distant loci. Therefore, there is a growing consensus on the requirement of multiple anti-(lymph)angiogenic molecules to stop cell invasion efficiently. Here we studied the cooperation between endogenous anti-angiogenic molecules, endostatin and fibstatin, and a chemokine, the Platelet Factor-4 variant 1, CXCL4L1. Anti-angiogenic factors were co-expressed by IRES-based bicistronic vectors and their cooperation was analyzed either by local delivery following transduction of pancreatic adenocarcinoma cells with lentivectors, or by distant delivery resulting from intramuscular administration in vivo of adeno-associated virus derived vectors followed by tumor subcutaneous injection. In this study, fibstatin and CXCL4L1 cooperate to inhibit endothelial cell proliferation, migration and tubulogenesis in vitro. No synergistic effect was found for fibstatin–endostatin combination. Importantly, we demonstrated for the first time that fibstatin and CXCL4L1 not only inhibit in vivo angiogenesis, but also lymphangiogenesis and tumor spread to the lymph nodes, whereas no beneficial effect was found on tumor growth inhibition using molecule combinations compared to molecules alone. These data reveal the synergy of CXCL4L1 and fibstatin in inhibition of tumor angiogenesis, lymphangiogenesis and metastasis and highlight the potential of IRES-based vectors to develop anti-metastasis combined gene therapies. |
| Databáze: | OpenAIRE |
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