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Signalling via vascular endothelial growth factor receptor‐3 is sufficient for lymphangiogenesis in transgenic mice
Author(s) -
Veikkola Tanja,
Jussila Lotta,
Makinen Taija,
Karpanen Terhi,
Jeltsch Michael,
Petrova Tatiana V.,
Kubo Hajime,
Thurston Gavin,
McDonald Donald M.,
Achen Marc G.,
Stacker Steven A.,
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/20.6.1223
Subject(s) - lymphangiogenesis , biology , angiogenesis , vascular endothelial growth factor c , microbiology and biotechnology , lymphatic system , vascular endothelial growth factor , vascular endothelial growth factor a , lymphatic endothelium , cancer research , paracrine signalling , receptor , signal transduction , immunology , metastasis , vegf receptors , cancer , biochemistry , genetics
Vascular endothelial growth factor receptor‐3 (VEGFR‐3) has an essential role in the development of embryonic blood vessels; however, after midgestation its expression becomes restricted mainly to the developing lymphatic vessels. The VEGFR‐3 ligand VEGF‐C stimulates lymphangiogenesis in transgenic mice and in chick chorioallantoic membrane. As VEGF‐C also binds VEGFR‐2, which is expressed in lymphatic endothelia, it is not clear which receptors are responsible for the lymphangiogenic effects of VEGF‐C. VEGF‐D, which binds to the same receptors, has been reported to induce angiogenesis, but its lymphangiogenic potential is not known. In order to define the lymphangiogenic signalling pathway we have created transgenic mice overexpressing a VEGFR‐3‐specific mutant of VEGF‐C (VEGF‐C156S) or VEGF‐D in epidermal keratinocytes under the keratin 14 promoter. Both transgenes induced the growth of lymphatic vessels in the skin, whereas the blood vessel architecture was not affected. Evidence was also obtained that these growth factors act in a paracrine manner in vivo . These results demonstrate that stimulation of the VEGFR‐3 signal transduction pathway is sufficient to induce specifically lymphangiogenesis in vivo .