Proteases and protease inhibitors in tumor progression.
Our understanding of the role of matrix degrading proteases in cancer has dramatically expanded over the last two decades. From correlative observations linking proteases to cancer progression, we have accumulated evidence supporting a causal role for proteases in various steps of tumor progression and have become increasingly aware of the complex interactions that exist among proteases. Specific natural inhibitors of these proteases have also been identified and their role as potent cytostatic agents in cancer has been suggested. In this article some of the concepts on the role of proteases in cancer are discussed and examples of cooperation between matrix metalloproteinases and the plasmin/plasminogen activators system are presented. The role of protease inhibitors such as tissue inhibitor of metalloproteinases-2 (TIMP-2) and plasminogen activator inhibitor-2 (PAI-2) as inhibitors of tumor growth, invasion and metastasis is discussed.
DeClerck
Y A
YA
Department of Pediatrics, Childrens Hospital Los Angeles, University of Southern California 90027, USA. ydeclerck%smtpgate@chlais.usc.edu
Imren
S
S
Montgomery
A M
AM
Mueller
B M
BM
Reisfeld
R A
RA
Laug
W E
WE
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D018450:Disease Progression; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D017396:Plasminogen Activator Inhibitor 2 / Q000494:pharmacology; D011480:Protease Inhibitors / Q000378:metabolism*; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology
D017396:Plasminogen Activator Inhibitor 2; D011480:Protease Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D010450:Endopeptidases; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases