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Local proteolytic activity in tumor cell invasion and metastasis
Author(s) -
Ludwig Thomas
Publication year - 2005
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.20306
Subject(s) - proteases , proteolytic enzymes , microbiology and biotechnology , angiogenesis , extracellular matrix , metastasis , matrix metalloproteinase , biology , cell migration , cancer cell , cell , tumor microenvironment , apoptosis , cell growth , cancer , cancer research , biochemistry , tumor cells , enzyme , genetics
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. BioEssays 27:1181–1191, 2005. © 2005 Wiley Periodicals, Inc.