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Open Access Highly Accessed Research article

MMP-9 expression varies according to molecular subtypes of breast cancer

Einas M Yousef1, Muhammad R Tahir2, Yves St-Pierre3 and Louis A Gaboury14*

Author Affiliations

1 Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada

2 Le centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Canada

3 INRS-Armand-Frappier, Université du Québec, Laval, Montréal, Canada

4 Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Canada

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BMC Cancer 2014, 14:609  doi:10.1186/1471-2407-14-609

Published: 23 August 2014

Abstract

Background

In 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients.

Methods

MMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.

Results

Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.

Conclusions

Differential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.

Keywords:
MMP-9; Human breast cancers; Metastasis; In silico analysis; Tissue microarrays