Clinical & Experimental Metastasis

, Volume 25, Issue 3, pp 265–272 | Cite as

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

Research Paper

Abstract

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.

Keywords

Connexin Bone Cancer MDA-MB-231 Osteoblasts Adhesion 

Notes

Acknowledgements

We thank Dr. Deborah S Grove for Real time RT-PCR technical support. This work was supported by the National Institutes of Health, National Cancer Institute grant R01-CA 90991.

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Division of Musculoskeletal Sciences, Department of Orthopaedics and RehabilitationThe Pennsylvania State University College of MedicineHersheyUSA

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