Alterations in Cx43 and OB-cadherin affect breast cancer cell metastatic potential

Emerging evidence suggests that gap junctional intercellular communication (GJIC) and expression of connexins (Cx) contribute to the metastatic potential of breast cancer cells. To more directly address this, an aggressive bone metastasis breast cancer cell line, MDA-MET (MET), was stably transfected with human Cx43 cDNA (MET/Cx43⁺). Focusing on clone 28 of MET/Cx43⁺, we demonstrated that GJIC, Cx43 protein and Cx43 mRNA were significantly increased in MET/Cx43⁺ cells relative to MET, the plasmid control for the Cx43 transfectants (MET/HY) and a metastatic breast cancer cell that is less metastatic to bone than MET, MDA-MB-231. Cx26 mRNA was also increased in MET/Cx43⁺ clone 28 cells while mRNA for Cx32, Cx37, Cx40 and Cx45 were not detected in any of the breast cancer cell lines examined. MET/Cx43⁺ clone 28 invasiveness was decreased by 33% relative to MET/HY, while their ability to migrate was unchanged. The ability of MET/Cx43⁺ clone 28 cells to adhere to hFOB and HUV-EC-C cells was decreased approximately 30% and 70%, respectively, relative to MET and MET/HY. E-cadherin and N-cadherin proteins were not detected in MET, MDA-MB-231, MET/Cx43⁺ clone 28 and MET/HY cells. However, OB-cadherin protein levels were decreased approximately 43% in MET/Cx43⁺ clone 28 relative to MET/HY cells. These findings suggest that GJIC and Cx43 expression contribute to breast cancer cell adhesion and migration, possibly through a mechanism involving OB-cadherin, and these changes in turn regulate the metastatic potential of breast cancer cells, especially to bone.