Role of stromelysin-3 in mammary tumor progression

Numerous studies have provided evidence that, although the transformation of epithelial cells is the sine qua non condition for the development of carcinomas, the nature of the connective/stromal tissue environment is crucial for tumor progression. Matrix metallo-proteinases (MMPs) that interact with stromal components have been shown to contribute to malignancy in both the early and late stages of tumor progression in human and mouse. Therefore, these studies are of interest to improve our understanding of malignant processes. In this context, the 11th member of the MMP family (MMP11), also named stromelysin-3 (ST3), fulfills this paradigm. It was discovered in 1990 because of its overexpression in a cDNA library established from a human breast cancer biopsy. Later, clinical trials showed that high levels of ST3 expression correlated with a lower survival rate among patients with breast, head and neck, or colon cancer. Therefore, the possibility that ST3 might play a role during tumor progression was promising for the diagnosis, prognosis and design of new treatment. During the past 10 years, numerous experiments have been performed to enhance the knowledge of the biological function of ST3, and to evaluate its clinical relevance. From the data, ST3 appears to be a unique member of the MMP family, exhibiting peculiar features and function.