Regulation of matrix metalloproteinases - their role in tumor invasion and metastasis.

In order for tumor cells to colonise secondary organs and tissues it is necessary for them to be able to complete all the essential steps of the metastatic cascade. We discuss here some of the important aspects of this process, highlighting those events likely to be important in the control of tumor cell invasion. The expression of matrix metalloproteinases (MMP) capable of degrading tissue matrix or basement membranes, constitutes an important feature of tumor cell escape from the primary neoplasm and entry into/ colonisation of the secondary body site. In particular, the balance between MMP and protease inhibitor expression will determine the invasive capacity of a cancer cell. The molecular control of gene expression, together with the molecules important in regulating the production of proteinases and their inhibitors is complex, and the important facets of these pathways are discussed. Cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and transforming growth factor-beta (TGF-beta), play a crucial role in modulating MMP-2 and MMP-9 expression, and these, together with other regulatory cytokines constitute an important mechanism whereby the tumor cells can increase their invasive potential through the secretion of proteases.