How intact is the basement membrane? Role of MMPs

Progression, invasion, and metastasis of tumor cells involve the degradation of the basement membrane (BM), caused by a class of proteases, the matrix metalloproteinases (MMPs). Aberrant MMP activity is the hallmark of many epithelial cancers such as the cervical, breast, and oral. Conventional cytological and histological techniques are insufficient to predict the course of the disease. Therefore, it is necessary to understand and evaluate the various factors contributing to tumor progression in these cancers. Overexpression of MMPs in cervical, oral, and breast cancers has been linked to enhanced tumor invasion and metastases in vitro and in vivo model systems. The expression of MMP-2 and MMP-9 proteins in premalignant lesions of the uterine cervix and infiltrating duct carcinomas of breast and invasive squamous cell carcinomas (SCCs) suggest a gradually increasing invasive potential. The vast literature on MMPs that initiate BM destruction and degradation of extracellular matrix components, suggest that these MMPs may play a role during tumor progression in epithelial tumors. It therefore appears that the measurement of MMPs would be a useful prognostic marker to assess the aggressiveness of the tumor and determine if they may metastasize. Also, these MMPs are crucial molecular targets that could be used for anticancer therapy. Metalloproteinase inhibitors (MMPI) are a new class of drugs which are in phase III clinical trials.