Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis.
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4164522?pdf=render |
| _version_ | 1818921670978568192 |
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| author | Ludovic Maertens Charlotte Erpicum Benoit Detry Silvia Blacher Bénédicte Lenoir Oriane Carnet Christel Péqueux Didier Cataldo Julie Lecomte Jenny Paupert Agnès Noel |
| author_facet | Ludovic Maertens Charlotte Erpicum Benoit Detry Silvia Blacher Bénédicte Lenoir Oriane Carnet Christel Péqueux Didier Cataldo Julie Lecomte Jenny Paupert Agnès Noel |
| author_sort | Ludovic Maertens |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T01:41:21Z |
| format | Article |
| id | doaj.art-32d86fd68de24932bfa9a3a3db390866 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T01:41:21Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-32d86fd68de24932bfa9a3a3db3908662022-12-21T19:57:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10697610.1371/journal.pone.0106976Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis.Ludovic MaertensCharlotte ErpicumBenoit DetrySilvia BlacherBénédicte LenoirOriane CarnetChristel PéqueuxDidier CataldoJulie LecomteJenny PaupertAgnès NoelIt 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.http://europepmc.org/articles/PMC4164522?pdf=render |
| spellingShingle | Ludovic Maertens Charlotte Erpicum Benoit Detry Silvia Blacher Bénédicte Lenoir Oriane Carnet Christel Péqueux Didier Cataldo Julie Lecomte Jenny Paupert Agnès Noel Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis. PLoS ONE |
| title | Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis. |
| title_full | Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis. |
| title_fullStr | Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis. |
| title_full_unstemmed | Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis. |
| title_short | Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis. |
| title_sort | bone marrow derived mesenchymal stem cells drive lymphangiogenesis |
| url | http://europepmc.org/articles/PMC4164522?pdf=render |
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