Endothelin-1 cooperates with hypoxia to induce vascular-like structures through vascular endothelial growth factor-C, -D and -A in lymphatic endothelial cells

Life Sciences
Emirena GarrafaFrancesca Spinella

Abstract

Lymphangiogenesis refers to the formation of new lymphatic vessels and is thought to constitute conduits for the tumor cells to metastasize. We previously demonstrated that endothelin (ET)-1 through its binding with ETB receptor (ET(B)R) expressed on lymphatic endothelial cells (LEC), induced cell growth and invasiveness. Since vascular endothelial growth factor (VEGF)-A/-C/-D, and hypoxia play key role in lymphatic differentiation, in this study we investigated the involvement of these growth factors and hypoxia in ET-1-induced lymphangiogenesis. Real time PCR and ELISA were used to quantify VEGF-A/-C/-D. LEC morphological differentiation was analyzed by tube formation assay on Matrigel. Hypoxia, as well as ET-1, induced an increase in VEGF-A/-C and -D expression that was reduced in the presence of a selective ET(B)R antagonist, BQ788, and enhanced when ET-1 was administered under hypoxic conditions. We analyzed the role of hypoxia on LEC morphological differentiation, and found that hypoxia increased the formation of vascular-like structures on Matrigel and that in combination with ET-1 this effect was markedly enhanced. The use of specific antibodies neutralizing VEGF-A, or recombinant VEGFR-3/(Flt-4)/Fc that block VEGF-C/-D...Continue Reading

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Citations

Sep 12, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Francesca SpinellaAnna Bagnato
Jan 31, 2017·Lymphatic Research and Biology·Fabio TorriEmirena Garrafa
Jun 28, 2018·Physiological Research·W LiA Ergul

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