Oncotarget

Research Papers:

Gap junction-mediated transfer of miR-145-5p from microvascular endothelial cells to colon cancer cells inhibits angiogenesis

Dominique Thuringer _, Gaetan Jego, Kevin Berthenet, Arlette Hammann, Eric Solary and Carmen Garrido

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Oncotarget. 2016; 7:28160-28168. https://doi.org/10.18632/oncotarget.8583

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Abstract

Dominique Thuringer1, Gaetan Jego1,2, Kevin Berthenet1, Arlette Hammann1, Eric Solary3, Carmen Garrido1,2,4

1INSERM, U866, Faculty of Medecine, 21000 Dijon, France

2University of Bourgogne-Franche-Comté, 21000 Dijon, France

3INSERM, U1170, Institut Gustave Roussy, 94508 Villejuif, France

4CGFL, BP77980, 21000 Dijon, France

Correspondence to:

Dominique Thuringer, email: dominique.thuringer@u-bourgogne.fr

Keywords: GJIC, Cx43, micro-RNA, tubulogenesis, colorectal tumor

Received: December 29, 2015     Accepted: March 28, 2016     Published: April 5, 2016

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.


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