Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers

Neoplastic growth and dissemination involve increased proteolytic activity that is able to escape the regulative elements. Matrix metalloproteinases (MMPs), particularly gelatinases A and B (MMP-2 and -9), play a role in tumor invasion and angiogenesis, and they participate in cancer progression in several neoplasias. The expression of tissue inhibitors of gelatinases, TIMPs-1 and -2, has also been shown to be associated with the clinical course in some cancers. The prognostic value of these markers, however, seems to vary a great deal in different neoplastic diseases. In this review, the impact of the gelatinases and their inhibitors on the clinical course in several solid cancers is evaluated based on the growing data from recent clinical studies. The clinical data most often explore the overexpression of mRNA or immunoreactive protein in tumor tissue, or measure the concentration of the circulating proteinase or its inhibitor in pretreatment or follow-up serum samples. The growing amount of recent clinical data suggests that the impact of gelatinases on treatment decisions should be tested in clinical trials.