title: Primary tumor- and metastasis-derived colon cancer cells differently modulate connexin expression and function in human capillary endothelial cells.
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.
authors: INSERM, U866 Faculty of Medecine, 21000 Dijon, France.
authors: Dominique
authors: D
authors: Thuringer
authors: University of Bourgogne-Franche-Comté, 21000 Dijon, France.
authors: Kevin
authors: K
authors: Berthenet
authors: CNRS ERL7368, STIM Lab, University of Poitiers, 86022 Poitiers, France.
authors: Laurent
authors: L
authors: Cronier
authors: INSERM, U1170, Institut Gustave Roussy, 94508 Villejuif, France.
authors: Eric
authors: E
authors: Solary
authors: INSERM, U866 Faculty of Medecine, 21000 Dijon, France.|University of Bourgogne-Franche-Comté, 21000 Dijon, France.|CGFL, 21000 Dijon, France.
authors: Carmen
authors: C
authors: Garrido
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D017629:Gap Junctions / Q000378:metabolism* / Q000473:pathology; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D009362:Neoplasm Metastasis; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D010766:Phosphorylation; D034622:RNA Interference; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D000097002:Gap Junction beta-1 Protein
chemical_list: D048948:14-3-3 Proteins; D000255:Adenosine Triphosphate; D018031:Connexin 43; D017630:Connexins; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D023063:Receptors, Interleukin-8B; D012694:Serine; D000097002:Gap Junction beta-1 Protein; C500216:GJA1 protein, human; C057725:HSPB1 protein, human
keywords: CXCR2; Cx32; Cx43; GJIC; HSP27