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VEGF receptor 2/‐3 heterodimers detected in situ by proximity ligation on angiogenic sprouts
Author(s) -
Nilsson Ingrid,
Bahram Fuad,
Li Xiujuan,
Gualandi Laura,
Koch Sina,
Jarvius Malin,
Söderberg Ola,
Anisimov Andrey,
Kholová Ivana,
Pytowski Bronislaw,
Baldwin Megan,
YläHerttuala Seppo,
Alitalo Kari,
Kreuger Johan,
ClaessonWelsh Lena
Publication year - 2010
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 - 10.1038/emboj.2010.30
Subject(s) - library science , cancer genetics , biology , medicine , genetics , cancer , computer science
The vascular endothelial growth factors VEGFA and VEGFC are crucial regulators of vascular development. They exert their effects by dimerization and activation of the cognate receptors VEGFR2 and VEGFR3. Here, we have used in situ proximity ligation to detect receptor complexes in intact endothelial cells. We show that both VEGFA and VEGFC potently induce formation of VEGFR2/‐3 heterodimers. Receptor heterodimers were found in both developing blood vessels and immature lymphatic structures in embryoid bodies. We present evidence that heterodimers frequently localize to tip cell filopodia. Interestingly, in the presence of VEGFC, heterodimers were enriched in the leading tip cells as compared with trailing stalk cells of growing sprouts. Neutralization of VEGFR3 to prevent heterodimer formation in response to VEGFA decreased the extent of angiogenic sprouting. We conclude that VEGFR2/‐3 heterodimers on angiogenic sprouts induced by VEGFA or VEGFC may serve to positively regulate angiogenic sprouting.