Extracellular HSP27 mediates angiogenesis through Toll-like receptor 3
| Autor: | Anne-Laure Joly, Nadhir Yousfi, Manuel Rosa-Calatrava, Adonis Hazoumé, Sophie Hébrard, André Bouchot, Guillaume Wettstein, Olivier Terrier, Eric Solary, Gaëtan Jego, Laurent Cronier, Carmen Garrido, Martin E. Gleave, Dominique Thuringer |
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| Rok vydání: | 2013 |
| Předmět: |
Vascular Endothelial Growth Factor A
Immunoprecipitation Angiogenesis HSP27 Heat-Shock Proteins Neovascularization Physiologic Biochemistry 03 medical and health sciences 0302 clinical medicine Hsp27 Genetics Extracellular Animals Secretion Receptor Molecular Biology Cells Cultured 030304 developmental biology 0303 health sciences biology NF-kappa B Endothelial Cells Cell migration Molecular biology Toll-Like Receptor 3 Chorioallantoic membrane Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein Calcium Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 27(10) |
| ISSN: | 1530-6860 |
| Popis: | The heat-shock protein 27 (HSP27) is up-regulated in tumor cells and released in their microenvironment. Here, we show that extracellular HSP27 has a proangiogenic effect evidenced on chick chorioallantoic membrane. To explore this effect, we test the recombinant human protein (rhHSP27) at physiopathological doses (0.1-10 μg/ml) onto human microvascular endothelial cells (HMECs) grown as monolayers or spheroids. When added onto HMECs, rhHSP27 dose-dependently accelerates cell migration (with a peak at 5 μg/ml) and favors spheroid sprouting within 12-24 h. rhHSP27 increases VEGF gene transcription and promotes secretion of VEGF-activating VEGF receptor type 2. Increased VEGF transcription is related to NF-κB activation in 30 min. All of these effects are initiated by rhHSP27 interaction with Toll-like receptor 3 (TLR3). Such an interaction can be detected by immunoprecipitation but does not seem to be direct, as we failed to detect an interaction between rhHSP27 and monomeric TLR3 by SPR analysis. rhHSP27 is rapidly internalized with a pool of TLR3 to the endosomal compartment (within 15-30 min), which is required for NF-κB activation in a cytosolic Ca(2+)-dependent manner. The HSP27/TLR3 interaction induces NF-κB activation, leading to VEGF-mediated cell migration and angiogenesis. Such a pathway provides alternative targets for antiangiogenic cancer therapy. |
| Databáze: | OpenAIRE |
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