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Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF‐C/D receptor VEGFR‐3
Author(s) -
Mäkinen Taija,
Veikkola Tanja,
Mustjoki Satu,
Karpanen Terhi,
Catimel Bruno,
Nice Edouard C.,
Wise Lyn,
Mercer Andrew,
Kowalski Heinrich,
Kerjaschki Dontscho,
Stacker Steven A.,
Achen Marc G.,
Alitalo Kari
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.17.4762
Subject(s) - biology , lymphatic endothelium , lymphatic system , vascular endothelial growth factor c , microbiology and biotechnology , vascular endothelial growth factor a , lymph node stromal cell , protein kinase b , cancer research , endothelium , kinase insert domain receptor , vascular endothelial growth factor b , vascular endothelial growth factor , immunology , signal transduction , endocrinology , vegf receptors
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.