Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis
| Autor: | Agnès Noël, Ludovic Maertens, Benoît Detry, Bénédicte Lenoir, Julie Lecomte, Jenny Paupert, Didier Cataldo, Silvia Blacher, Charlotte Erpicum, Oriane Carnet, Christel Pequeux |
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| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cell signaling Angiogenesis lcsh:Medicine Signal transduction chemistry.chemical_compound Mice Cell Movement Animal Cells Medicine and Health Sciences Lymphangiogenesis Phosphorylation lcsh:Science Multidisciplinary Stem Cells VEGF signaling Vascular endothelial growth factor Endothelial stem cell Vascular endothelial growth factor A Lymphatic Endothelium Cell Motility Lymphatic system Cell Processes Female Anatomy Cellular Types Research Article medicine.medical_specialty Cell biology MAP Kinase Signaling System government.form_of_government Biology Lymphatic System Paracrine signalling Internal medicine medicine Animals Cell Proliferation Biology and life sciences lcsh:R Endothelial Cells Mesenchymal Stem Cells Mice Inbred C57BL Endocrinology Receptors Vascular Endothelial Growth Factor chemistry Culture Media Conditioned Cancer research government lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 9, p e106976 (2014) |
| ISSN: | 1932-6203 |
| Popis: | It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2. |
| Databáze: | OpenAIRE |
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