Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF‐C/D receptor VEGFR‐3
Identifieur interne : 009E83 ( Main/Exploration ); précédent : 009E82; suivant : 009E84Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF‐C/D receptor VEGFR‐3
Auteurs : Taija M Kinen [Finlande] ; Tanja Veikkola [Finlande] ; Satu Mustjoki [Finlande] ; Terhi Karpanen [Finlande] ; Bruno Catimel [Australie] ; Edouard C. Nice [Australie] ; Lyn Wise [Nouvelle-Zélande] ; Andrew Mercer [Nouvelle-Zélande] ; Heinrich Kowalski [Autriche] ; Dontscho Kerjaschki [Autriche] ; Steven A. Stacker [Australie] ; Marc G. Achen [Australie] ; Kari Alitalo [Finlande]Source :
- The EMBO Journal [ 0261-4189 ] ; 2001-09-03.
Abstract
Vascular endothelial growth factor receptor‐3 (VEGFR‐3/Flt4) binds two known members of the VEGF ligand family, VEGF‐C and VEGF‐D, and has a critical function in the remodelling of the primary capillary vasculature of midgestation embryos. Later during development, VEGFR‐3 regulates the growth and maintenance of the lymphatic vessels. In the present study, we have isolated and cultured stable lineages of blood vascular and lymphatic endothelial cells from human primary microvascular endothelium by using antibodies against the extracellular domain of VEGFR‐3. We show that VEGFR‐3 stimulation alone protects the lymphatic endothelial cells from serum deprivation‐induced apoptosis and induces their growth and migration. At least some of these signals are transduced via a protein kinase C‐dependent activation of the p42/p44 MAPK signalling cascade and via a wortmannin‐sensitive induction of Akt phosphorylation. These results define the critical role of VEGF‐C/VEGFR‐3 signalling in the growth and survival of lymphatic endothelial cells. The culture of isolated lymphatic endothelial cells should now allow further studies of the molecular properties of these cells.
Url:
DOI: 10.1093/emboj/20.17.4762
Affiliations:
- Australie, Autriche, Finlande, Nouvelle-Zélande
- Uusimaa, Vienne (Autriche)
- Helsinki, Vienne (Autriche)
- Université d'Helsinki
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Later during development, VEGFR‐3 regulates the growth and maintenance of the lymphatic vessels. In the present study, we have isolated and cultured stable lineages of blood vascular and lymphatic endothelial cells from human primary microvascular endothelium by using antibodies against the extracellular domain of VEGFR‐3. We show that VEGFR‐3 stimulation alone protects the lymphatic endothelial cells from serum deprivation‐induced apoptosis and induces their growth and migration. At least some of these signals are transduced via a protein kinase C‐dependent activation of the p42/p44 MAPK signalling cascade and via a wortmannin‐sensitive induction of Akt phosphorylation. These results define the critical role of VEGF‐C/VEGFR‐3 signalling in the growth and survival of lymphatic endothelial cells. The culture of isolated lymphatic endothelial cells should now allow further studies of the molecular properties of these cells.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Autriche</li><li>Finlande</li><li>Nouvelle-Zélande</li></country><region><li>Uusimaa</li><li>Vienne (Autriche)</li></region><settlement><li>Helsinki</li><li>Vienne (Autriche)</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Finlande"><noRegion><name sortKey="M Kinen, Taija" sort="M Kinen, Taija" uniqKey="M Kinen T" first="Taija" last="M Kinen">Taija M Kinen</name></noRegion><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Karpanen, Terhi" sort="Karpanen, Terhi" uniqKey="Karpanen T" first="Terhi" last="Karpanen">Terhi Karpanen</name><name sortKey="Mustjoki, Satu" sort="Mustjoki, Satu" uniqKey="Mustjoki S" first="Satu" last="Mustjoki">Satu Mustjoki</name><name sortKey="Veikkola, Tanja" sort="Veikkola, Tanja" uniqKey="Veikkola T" first="Tanja" last="Veikkola">Tanja Veikkola</name></country><country name="Australie"><noRegion><name sortKey="Catimel, Bruno" sort="Catimel, Bruno" uniqKey="Catimel B" first="Bruno" last="Catimel">Bruno Catimel</name></noRegion><name sortKey="Achen, Marc G" sort="Achen, Marc G" uniqKey="Achen M" first="Marc G." last="Achen">Marc G. Achen</name><name sortKey="Nice, Edouard C" sort="Nice, Edouard C" uniqKey="Nice E" first="Edouard C." last="Nice">Edouard C. Nice</name><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A." last="Stacker">Steven A. Stacker</name></country><country name="Nouvelle-Zélande"><noRegion><name sortKey="Wise, Lyn" sort="Wise, Lyn" uniqKey="Wise L" first="Lyn" last="Wise">Lyn Wise</name></noRegion><name sortKey="Mercer, Andrew" sort="Mercer, Andrew" uniqKey="Mercer A" first="Andrew" last="Mercer">Andrew Mercer</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Kowalski, Heinrich" sort="Kowalski, Heinrich" uniqKey="Kowalski H" first="Heinrich" last="Kowalski">Heinrich Kowalski</name></region><name sortKey="Kerjaschki, Dontscho" sort="Kerjaschki, Dontscho" uniqKey="Kerjaschki D" first="Dontscho" last="Kerjaschki">Dontscho Kerjaschki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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