Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3

Taija Makinen, Tanja Veikkola, Satu Mustjoki, Terhi Karpanen, Bruno Catimel, Edouard Nice, Lyn Wise, Andrew Mercer, Heinrich Kowalski, Dontscho Kerjaschki, Steven A Stacker, Marc G Achen, Kari Alitalo

Research output: Contribution to journalArticleResearchpeer-review

630 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4762 - 4773
Number of pages12
JournalThe EMBO Journal
Volume20
Issue number17
Publication statusPublished - 2001

Cite this