Research article

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

Gwladys Zabouo^1,2 , Anne-Marie Imbert^1,2 , Jocelyne Jacquemier^3,4 , Pascal Finetti⁴ , Thomas Moreau^1,2 , Benjamin Esterni² , Daniel Birnbaum⁴ , François Bertucci^2,4,5,6 and Christian Chabannon^1,2,6,7

¹  Institut Paoli-Calmettes, Centre de Ressources Biologiques en Oncologie, Centre de Thérapie Cellulaire et Génique, Marseille 13009, France

²  Inserm U891, Centre de Recherche en Cancérologie de Marseille, Equipe Recherche Clinique, Marseille 13009, France

³  Institut Paoli-Calmettes, Département de Bio-pathologie, Marseille 13009, France

⁴  Inserm U891, Centre de Recherche en Cancérologie de Marseille, Equipe Oncologie Moléculaire, Marseille 13009, France

⁵  Institut Paoli-Calmettes, Département de Médecine, Marseille 13009, France

⁶  Université de la Méditerranée, Marseille 13007, France

⁷  Inserm CIC-B510, Centre d'Investigations Cliniques en Biothérapie, Marseille 13009, France

author email corresponding author email

Breast Cancer Research 2009, 11:R1doi:10.1186/bcr2215

Published:	5 January 2009

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.