Oncotarget

Research Papers:

Primary tumor- and metastasis-derived colon cancer cells differently modulate connexin expression and function in human capillary endothelial cells

Dominique Thuringer _, Kevin Berthenet, Laurent Cronier, Eric Solary and Carmen Garrido

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Oncotarget. 2015; 6:28800-28815. https://doi.org/10.18632/oncotarget.4894

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Abstract

Dominique Thuringer1, Kevin Berthenet2, Laurent Cronier3, Eric Solary4, Carmen Garrido1,2,5

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

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

3CNRS ERL7368, STIM Lab, University of Poitiers, 86022 Poitiers, France

4INSERM, U1170, Institut Gustave Roussy, 94508 Villejuif, France

5CGFL, 21000 Dijon, France

Correspondence to:

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

Keywords: GJIC, Cx32, Cx43, HSP27, CXCR2

Received: May 08, 2015     Accepted: July 24, 2015     Published: August 06, 2015

ABSTRACT

A gradual loss of functional gap junction between tumor cells has been reported with colorectal cancer (CRC) progression. Here, we explored if colon cancer cells could also affect gap junctions in blood capillary cells. Human microvascular endothelial cells (HMEC) were cultured with two CRC cell lines established from a unique patient. SW480 cells, derived from the primary tumor, migrate much faster across HMEC monolayer than SW620 cells derived from a metastatic site. The motile SW480 cells highly express and release HSP27 that increases gap junction formation with HMEC. Soluble HSP27 phosphorylates the connexin Cx43 on serine residues and induces its interaction with the oncoprotein 14-3-3, which promotes Cx43 delivery at the plasma membrane. The factors secreted by less motile SW620 cells do not affect Cx43 expression but up-regulate the expression of the connexin Cx32 through an activation of the chemokine receptor CXCR2. In turn, SW620 secreted factors induce tubulogenesis and ATP release. Altogether, cell lines derived from CRC primary tumor and metastasis differentially adapt endothelial cell functions by modulating connexin expression through released mediators.


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