Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloproteinases in cancer.

Over the last few years a growing number of matrix degrading metalloproteinases have been implicated in cancer. These include in particular the matrix metalloproteinases (MMPs) which have been shown to be associated with a large variety of human malignancies, and the metalloproteinases with a disintegrin domain (ADAMs) whose potential role in cancer has begun to be examined. The expression of MMPs in human cancer is the result of a complex interaction between tumour cells and non-malignant stromal cells including fibroblasts, endothelial cells and inflammatory cells which all actively participate in the production of MMPs in tumour tissue. The proteolytic modification of the extracellular matrix by these proteases does more than allow malignant cells to locally invade and form distant metastasis. It significantly alters the tumour micro-environment and modifies the contacts between tumour cells and extracellular matrix proteins. These changes can affect essential cellular functions such as growth, survival, migration and even drug resistance. As our understanding of the nature of the contacts between tumour cells and a proteolytically modified extracellular matrix continues to progress, it is likely that novel therapeutic approaches to modify tumour cell behaviour will be identified.