Expression of connexin43 in breast cancer cells (MDA-MB-231) :implications in cancer metastasis -

Abstract

Background: Connexins regulate cell proliferation, function and differentiation. Several human diseases are linked to mutations or dysfunction of connexin protein, and shown to be implicated in carcinogenic processes. For instance, a variety of breast cancer cell lines were shown to express low levels of connexin, or to lose the proper assembly of gap junctions. Several studies have reported channel-dependent and independent roles of connexin in tumorigenesis. A solid base was established proving that connexins are tumor suppressive proteins. Hypothesis: Over-expression of connexin43 (Cx43) decreases the metastatic potential of a breast cancer cell line MDA-MB-231, while its knock down by shRNA enhances their invasive properties. Materials and Methods: Upon over-expressing or down-regulating Cx43 in MDA-MB-231, metastatic abilities such as cell proliferation, cell aggregates’ morphology in 3D culture system, invasive potential and localization of β-catenin were assessed in vitro. In vivo, tumor onset and volume, survival rate and cancer cell infiltration to secondary metastatic sites were investigated in immunocompromised mice injected subdermally with cells over-expressing or down-regulating Cx43. Results: We have observed an epithelial phenotype with a suppressed potential to infiltrate lung and liver tissues upon Cx43 over-expression. On the other hand, Cx43 down-regulation induced a mesenchymal phenotype with higher expression levels of vascular endothelial growth factor (VEGF), invasive abilities and infiltration to secondary metastatic organ sites.Conclusion: Cx43 over-expression in MDA-MB-231 breast cancer cell line suppresses its metastatic potential in vivo and induces an epithelial phenotype in vitro. On the other hand, knocking down Cx43 induces a mesenchymal phenotype with aggressive invasive abilities.