Local proteolytic activity in tumor cell invasion and metastasis.
Proteolytic cleavage of extracellular matrix (ECM) is a critical regulator of many physiological and pathological events. It affects fundamental processes such as cell growth, differentiation, apoptosis and migration. Most proteases are produced as inactive proenzymes that undergo proteolytic cleavage for activation. Proteolytic activity is additionally modified by endogenous inhibitors. Mechanisms that localize and concentrate protease activity in the pericellular microenvironment of cells are prerequisites for processes like angiogenesis, bone development, inflammation and tumor cell invasion. Methods that enable real-time, high-resolution imaging and precise quantification of local proteolytic activity in vitro and in vivo remain major challenges. These methods will play an important role in the understanding of basic principles e.g. in cancer cell invasion, the identification of new therapeutical targets and hence drug design. This review highlights mechanisms and functions of local proteolytic activity with special emphasis on tumor cell invasion and metastasis, and focuses on techniques for the investigation of this process.
Ludwig
Thomas
T
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven Connecticut 06520-8026, USA. thomas.ludwig@yale.edu
D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D011480:Protease Inhibitors / Q000494:pharmacology; D015398:Signal Transduction
D011480:Protease Inhibitors; D010450:Endopeptidases