THE EXPRESSION LEVEL OF MATRIX METALLOPROTEINASES [2, 9] AND THEIR INHIBITORS IN BREAST CANCER

Abstract

Breast cancer is one of the most common malignant tumors in women. The clinical outcome of breast cancer depends on the extent of its local and metastatic spread. Invasion and metastasis are the major cause of cancer morbidity and mortality. The degradation of ECM is an important step of the metastatic cascade which needs active proteolytic enzymes as, serine proteases, cysteine proteases, and matrix metalloproteinases (MMPs). MMPs are a family of secreted or transmembrane zmc dependent endopeptidases with broad spectrum proteolytic activity for most classes of ECM proteins. They are secreted as latent form which needs activation by proteolytic cleavage. According to their domain structure they are divided into 6 subgroups including 16 family members which are produced by different genes. The net activity of MMPs is determined by the amount of proenzyme expressed, the extent to which the proenzyme is activated, and the local concentration of specific inhibitor. MMPs are inhibited by natural tissue inhibitors of metalloproteinases (TIMPs). The balance between MMPs and TIMPs is critical in maintaining the integrity of the ECM and its regulatory role in organ development, cell growth, and differentiation. The loss of balance has been implicated in several diseases, as rheumatoid arthritis, osteoarthritis, and cancer cell invasion and metastasis.