title: The gap junction protein Cx43 is involved in the bone-targeted metastatic behaviour of human prostate cancer cells.
abstract: For decades, cancer was associated with gap-junction defects. However, more recently it appeared that the gap junction proteins (connexins) could be re-expressed and participate to cancer cell dissemination during the late stages of tumor progression. Since primary tumors of prostate cancer (PCa) are known to be connexin deficient, it was interesting to verify whether their bone-targeted metastatic behaviour could be influenced by the re-expression of the connexin type (connexin43) which is originally present in prostate tissue and highly expressed in bone where it participates to the differentiation of osteoblastic cells. Thus, we investigated the effect of the increased Cx43 expression, by retroviral infection, on the metastatic behaviour of two well-characterized cell lines (PC-3 and LNCaP) representing different stages of PCa progression. It appeared that Cx43 differently behaved in those cell lines and induced different phenotypes. In LNCaP, Cx43 was functional, localized at the plasma membrane and its high expression was correlated with a more aggressive phenotype both in vitro and in vivo. In particular, those Cx43-expressing LNCaP cells exhibited a high incidence of osteolytic metastases generated by bone xenografts in mice. Interestingly, LNCaP cells were also able to decrease the proliferation of cocultured osteoblastic cells. In contrast, the increased expression of Cx43 in PC-3 cells led to an unfunctional, cytoplasmic localization of the protein and was correlated with a reduction of proliferation, adhesion and invasion of the cells. In conclusion, the localization and the functionality of Cx43 may govern the ability of PCa cells to metastasize in bones.
authors.affiliation: CNRS, UMR6187, Institute of Cellular Physiology and Biology, University of Poitiers, Poitiers Cedex, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Lamiche
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clarhaut
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Strale
authors.forename: Sophie
authors.initials: S
authors.lastname: Crespin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pedretti
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Bernard
authors.forename: Christian C
authors.initials: CC
authors.lastname: Naus
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Chen
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.forename: Norah
authors.initials: N
authors.lastname: Defamie
authors.forename: Marc
authors.initials: M
authors.lastname: Mesnil
authors.forename: Françoise
authors.initials: F
authors.lastname: Debiais
authors.forename: Laurent
authors.initials: L
authors.lastname: Cronier
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000503:physiopathology / Q000556:secondary*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D018031:Connexin 43 / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018031:Connexin 43
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