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Breast Cancer Research
Published in: Breast Cancer Research 1/2009

Open Access 01-06-2009 | Research article

CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines

Authors: Gwladys Zabouo, Anne-Marie Imbert, Jocelyne Jacquemier, Pascal Finetti, Thomas Moreau, Benjamin Esterni, Daniel Birnbaum, François Bertucci, Christian Chabannon

Published in: Breast Cancer Research | Issue 1/2009

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Abstract

Introduction

Metastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell–cell and cell–matrix interactions. CD146 (MCAM) is associated with an advanced tumor stage in melanoma, prostate cancer and ovarian cancer. Studies of CD146 expression and function in breast cancer remain scarce except for a report concluding that CD146 could act as a tumor suppressor in breast carcinogenesis.

Methods

To resolve these apparent discrepancies in the role of CD146 in tumor cells, we looked at the association of CD146 expression with histoclinical features in human primary breast cancers using DNA and tissue microarrays. By flow cytometry, we characterized CD146 expression on different breast cancer cell lines. Using siRNA or shRNA technology, we studied functional consequences of CD146 downmodulation of MDA-MB-231 cells in migration assays. Wild-type, mock-transfected and downmodulated transfected cells were profiled using whole-genome DNA microarrays to identify genes whose expression was modified by CD146 downregulation.

Results

Microarray studies revealed the association of higher levels of CD146 with histoclinical features that belong to the basal cluster of human tumors. Expression of CD146 protein on epithelial cells was detected in a small subset of cancers with histoclinical features of basal tumors. CD146+ cell lines displayed a mesenchymal phenotype. Downmodulation of CD146 expression in the MDA-MB-231 cell line resulted in downmodulation of vimentin, as well as of a set of genes that include both genes associated with a poor prognosis in a variety of cancers and genes known to promote cell motility. In vitro functional assays revealed decreased migration abilities associated with decreased CD146 expression.

Conclusions

In addition to its expression in the vascular compartment, CD146 is expressed on a subset of epithelial cells in malignant breast. CD146 may directly or indirectly contribute to tumor aggressiveness by promoting malignant cell motility. Changes in molecular signatures following downmodulation of CD146 expression suggest that CD146 downmodulation is associated with the reversal of several biological characteristics associated with epithelial to mesenchymal transition, and the phenomenon associated with the metastatic process.
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Metadata
Title
CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines
Authors
Gwladys Zabouo
Anne-Marie Imbert
Jocelyne Jacquemier
Pascal Finetti
Thomas Moreau
Benjamin Esterni
Daniel Birnbaum
François Bertucci
Christian Chabannon
Publication date
01-06-2009
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2009
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2215

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