Jornal de Carcinogênese e Mutagênese

Abstrato

Clinical Relevance of Matrix Metalloproteases and their Inhibitors in Breast Cancer

Noemí Eiró, Belen Fernandez-Garcia, Luis O González and Francisco J Vizoso

Degradation of the stromal connective tissue and basement membrane components are key elements in tumor invasion and metastasis. Some components, particularly the interstitial collagens, are very resistant to proteolytic attacks and can be degraded by specific proteinases like Matrix Metalloproteinases (MMPs). MMPs can also impact on tumor cell behavior in vivo as a consequence of their ability to cleave growth factors, cell surface receptors, cell adhesion molecules, or chemokines/cytokines, and for stimulating angiogenesis. Different molecular expression profiles of MMPs and their inhibitors (TIMPs) have been associated with the main steps in breast cancer progression, such as creating a potential invasive phenotype in Ductal Carcinoma in situ (DCIS), favoring the hematogenous dissemination, and enabling the metastatic progression across the axillary lymphatic system. These associations have clinical interests, as they can contribute to a better characterization of early breast carcinomas (which differ in their both biological and clinical behavior), evaluate microinvasion in resection specimens of breast tumors, provide a more precise prognostic, and predict the tumoral status of non-sentinel lymph nodes in breast cancer. It is also especially remarkable the evidences indicating that MMPs and TIMPs expression in individual cell populations from tumor stroma, such as mononuclear inflammatory cells (MICs) and fibroblast, clearly impacts on the clinical outcome of breast cancer patients. There are several factors linking inflammation, MMP activity and breast cancer. This knowledge will be useful to develop novel therapies and prevention strategies targeting critical components.