Role of proteases in tumor invasion and metastasis

Cancer remains a major cause of worldwide deaths due to ability of cancer cells to form secondary tumors at other sites by multistep process called metastasis. In order to migrate from their original site, tumor cells have to cross several barriers like basement membranes, interstitial tissues and extracellular matrices, which are composed primarily of collagen, proteoglycans, elastin, laminin and other glycoproteins. Tumor cells over express and secrete proteases which are capable of degrading the components of these barriers and thus facilitate their migration. The classes of proteases which have been implicated in the process of tumor invasion and metastasis include metalloproteases, serine proteases and cathepsins. Cancer cells in general have elevated levels of proteases belonging to more than one class. In some studies, process of invasion has been inhibited by using specific inhibitors of these proteases. Expression of some proteases has been observed only in some specific tumors. These proteases have been proposed to be of diagnostic/prognostic value. However a better understanding of the process of metastasis and tumor invasion is required before proteases can be used as therapeutic targets for blocking the spread of cancer.