title: Gap junction-mediated transfer of miR-145-5p from microvascular endothelial cells to colon cancer cells inhibits angiogenesis.
abstract: Gap junctional communication between cancer cells and blood capillary cells is crucial to tumor growth and invasion. Gap junctions may transfer microRNAs (miRs) among cells. Here, we explore the impact of such a transfer in co-culture assays, using the antitumor miR-145 as an example. The SW480 colon carcinoma cells form functional gap junction composed of connexin-43 (Cx43) with human microvascular endothelial cells (HMEC). When HMEC are loaded with miR-145-5p mimics, the miR-145 level drastically increases in SW480. The functional inhibition of gap junctions, using either a gap channel blocker or siRNA targeting Cx43, prevents this increase. The transfer of miR-145 also occurs from SW480 to HMEC but not in non-contact co-cultures, excluding the involvement of soluble exosomes. The miR-145 transfer to SW480 up-regulates their Cx43 expression and inhibits their ability to promote angiogenesis. Our results indicate that the gap junctional communication can inhibit tumor growth by transferring miRs from one endothelial cell to neighboring tumor cells. This "bystander" effect could find application in cancer therapy.
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Thuringer
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.|University of Bourgogne-Franche-Comté, 21000 Dijon, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Jego
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Berthenet
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.affiliation: INSERM, U1170, Institut Gustave Roussy, 94508 Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.affiliation: INSERM, U866, Faculty of Medecine, 21000 Dijon, France.|University of Bourgogne-Franche-Comté, 21000 Dijon, France.|CGFL, BP77980, 21000 Dijon, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs
keywords: Cx43; GJIC; colorectal tumor; micro-RNA; tubulogenesis