Cancer metastasis: biological and clinical aspects.

The main cause of morbidity and mortality in cancer is the formation of distant metastases. While alterations in c-oncogenes, tumour suppressor genes and DNA repair enzymes are the key molecules involved in carcinogenesis, increased expression of proteases, motility factors and altered expression of adhesion molecules are causally involved in metastasis. The proteases mediating metastasis include urokinase plasminogen activator, cathepsin B, D and L and various matrix metalloproteinases. Certain proteases involved in metastasis (e.g., urokinase plasminogen activator) have been shown to be strong and independent prognostic markers for a variety of cancers. Finally, molecules involved in cancer spread are potential targets for new forms of anti-metastatic therapies.