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Breast Cancer Research
Published in: Breast Cancer Research 4/2005

Open Access 01-08-2005 | Research article

Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture

Authors: Mary-Ann Pollmann, Qing Shao, Dale W Laird, Martin Sandig

Published in: Breast Cancer Research | Issue 4/2005

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Abstract

Introduction

Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells.

Method

To test this hypothesis we expressed connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and examined their ability to form gap junctions, establish heterocellular GJIC and migrate through monolayers of human microvascular endothelial cells (HMVEC) grown on matrigel-coated coverslips.

Results

HBL100 cells expressing Cx43 formed functional heterocellular gap junctions with HMVEC monolayers within 30 minutes. In addition, immunocytochemistry revealed Cx43 localized to contact sites between Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing cells compared to empty vector control cells. The expression of a functionally inactive Cx43 chimeric protein in HBL100 cells failed to increase migration efficiency, suggesting that the observed up-regulation of diapedesis in Cx43 expressing cells required heterocellular GJIC. This finding is further supported by the observation that blocking homocellular and heterocellular GJIC with carbenoxolone in co-cultures also reduced diapedesis of Cx43 expressing HBL100 tumor cells.

Conclusion

Collectively, our results suggest that heterocellular GJIC between breast tumor cells and endothelial cells may be an important regulatory step during metastasis.
Appendix
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Metadata
Title
Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture
Authors
Mary-Ann Pollmann
Qing Shao
Dale W Laird
Martin Sandig
Publication date
01-08-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1042

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