The vesicular transfer of CLIC1 from glioblastoma to microvascular endothelial cells requires TRPM7
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Dominique Thuringer1,2, Gaetan Chanteloup1,2, Pascale Winckler3 and Carmen Garrido1,2,4
1INSERM U1231, Laboratory of Excellence Ligue Nationale contre le Cancer, 21000 Dijon, France
2Université de Bourgogne Franche Comté, 21000 Dijon, France
3AgroSup Dijon, PAM UMR, DImaCell Imaging Facility, Université de Bourgogne Franche Comté, 21000 Dijon, France
4Centre Georges François Leclerc (CGFL), 21000 Dijon, France
Dominique Thuringer, email: firstname.lastname@example.org
Keywords: chloride intracellular channel; microRNA; exosome; transient receptor potential melastatin; glioblastoma
Received: April 23, 2018 Accepted: August 16, 2018 Published: September 07, 2018
Chloride intracellular channel 1 (CLIC1) is highly expressed and secreted by human glioblastoma cells and cell lines such as U87, initiating cell migration and tumor growth. Here, we examined whether CLIC1 could be transferred to human primary microvascular endothelial cells (HMEC). We previously reported that the oncogenic microRNA, miR-5096, increased the release of extracellular vesicles (EVs) by which it increased its own transfer from U87 to surrounding cells. Thus, we also examined its effect on the CLIC1 transfer. In homotypic cultures, miR-5096 did not increase the expression of CLIC1 in U87 nor in HMEC. However, the endothelial CLIC1 level increased after exposure to EVs released by U87, and even more by miR-5096-loaded U87. The EVs-transferred CLIC1 was active in HMEC, promoting endothelial sprouting in matrigel. Cell exposure to EVs induced cytosolic Ca2+ spikes which were dependent on the transient receptor potential melastatin member 7 (TRPM7). TRPM7 silencing prevented Ca2+ spikes and the subsequent CLIC1 delivery into HMEC. Our data suggest that the vesicular transfer of CLIC1 between cells requires TRMP7 expression in recipient endothelial cells. How the vesicular transfer of CLIC1 is modulated in cancer therapy is a future challenge.
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