Cell motility affects the intensity of gap junctional coupling in prostate carcinoma and melanoma cell populations

Abstract

Abstract. Connexins and gap junctions play a crucial role during carcinogenesis. While diverse regulatory systems have been shown to modulate their function, the influence of cell motility on the intensity of gap junctional intercellular coupling has yet to be systematically addressed. Since cancer cell motility and intercellular coupling determine cancer development, we aimed at elucidating how mutual cell translocation modulates the intensity of gap junctional coupling in cell populations. Time-lapse analyses of the motility of connexin43 (Cx43)-coupled rat prostate carcinoma (MAT-LyLu) and mouse melanoma (B16) cells cultured on hyper-adhesive substrata revealed a reduced intensity of intercellular translocations in the two cell populations compared to the control conditions. While no detectable effects on the architecture of the actin cytoskeleton and Cx43 expression and phosphorylation were observed, the inhibition of cell motility was paralleled by an increase in the abundance of Cx43-positive plaques in cell-to-cell contacts and an enhancement of gap junctional coupling in cell populations cultured on hyper-adhesive substrata. Thus, a direct correlation between two cellular parameters crucial for carcinogenesis, i.e. cell motility and gap junctional coupling intensity exists in cancer cell populations.

Invasive Cx43high sub-line of human prostate DU145 cells displays increased nanomechanical deformability

“…For Western blot analyses, the DU145 cell cultures were dissolved in lysis buffer and cellular proteins were applied to 15% SDS-polyacrylamide gels, followed by their transfer to nitrocellulose membranes. Blots were exposed to primary rabbit polyclonal anti-Cx43 and mouse monoclonal anti-a-tubulin antibody (both from Sigma) followed by detection of the antibodies using HRP-labelled secondary antibodies (Invitrogen) and a SuperSignal West Pico Substrate (Pierce, Rockford, IL) (Daniel-Wojcik et al, 2008). siRNA inhibition of Cx43 expression.…”

Connexins in melanoma: Potential role of Cx46 in its aggressiveness

“…Regardless of whether the expression of Cx43 increases or decreases in human melanoma, it is clear that when Cx43 is present in melanoma cells, there is a decrease in some parameters associated with the metastatic process. Thus, for example, murine B16 melanoma cells exposed to hyper-adhesive substrates develop increased levels of Cx43-GJIC, which is associated with inhibition of cancer cell motility, suggesting that Cx43 could modulate the migration capacity involved in melanoma carcinogenesis (Daniel-Wójcik et al, 2008).…”