Endogenous Regulators of Matrix Metalloproteinase Expression and Activity in Breast Cancers

Abstract

Tumour metastasis and secondary tumour formation are the leading causes behind breast cancer mortality. Modulation of matrix metalloproteinase (MMP) expression and activity promotes tumour metastasis and secondary tumour formation in numerous cancers including breast cancers. Extracellular matrix metalloproteinase inducer (EMMPRIN) and membrane type-1 matrix metalloproteinase (MT1-MMP) are endogenous molecules which regulate MMP expression and activity. Our current study examines the importance of EMMPRIN (also known as Basigin or CD147) and MT1-MMP (MMP-14) with particular reference to their roles in regulating MMP expression and activity in breast cancers. MT1-MMP and EMMPRIN expression levels are increased in invasive breast cancers and correspond to an invasive phenotype and a worse prognosis by various mechanisms including by causing an increase in MMP expression and activity. MT1-MMP also plays an important role in localization of MMP-2 to the tumour cell surface, regulating proteolysis at the cell-ECM interface. Determination of MT1-MMP and EMMPRIN expression levels could act as possible biomarkers for breast cancers and may help clinicians to better diagnose the stage of the cancer. Therapies involving inhibition of MMP expression and activity to downregulate invasive potential in breast cancers could thus involve the targeting of not just MMPs but also of their endogenous inhibitors EMMPRIN and MT1-MMP for increased efficiency.