Correction: Oncogenic extracellular HSP70 disrupts the gap-junctional coupling between capillary cells
High levels of circulating heat shock protein 70 (HSP70) are detected in many cancers. In order to explore the effects of extracellular HSP70 on human microvascular endothelial cells (HMEC), we initially used gap-FRAP technique. Extracellular human HSP70 (rhHSP70), but not rhHSP27, blocks the gap-junction intercellular communication (GJIC) between HMEC, disrupts the structural integrity of HMEC junction plaques, and decreases connexin43 (Cx43) expression, which correlates with the phosphorylation of Cx43 serine residues. Further exploration of these effects identified a rapid transactivation of the Epidermal Growth Factor Receptor in a Toll-Like Receptor 4-dependent manner, preceding its in…
Extracellular HSP27 mediates angiogenesis through Toll-like receptor 3.
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…
Oncogenic extracellular HSP70 disrupts the gap-junctional coupling between capillary cells
// Dominique Thuringer 1 , Kevin Berthenet 1 , Laurent Cronier 2 , Gaetan Jego 1,3 , Eric Solary 4 , Carmen Garrido 1,3,5 1 INSERM, U866, Faculty of Medecine, Dijon, France 2 CNRS ERL7368, STIM Lab, University of Poitiers, Poitiers, France 3 University of Burgundy, Dijon, France 4 INSERM, U1009, Institut Gustave Roussy, Villejuif, France 5 CGFL, BP77980 21000 Dijon, France Correspondence to: Dominique Thuringer, email: // Keywords : HSP, Cx43, pannexin, Ca 2+ oscillations, ATP release Received : January 30, 2015 Accepted : February 17, 2015 Published : March 10, 2015 Abstract High levels of circulating heat shock protein 70 (HSP70) are detected in many cancers. In order to explore the effec…