Cysteine proteinases and metastasis.
Cysteine proteinases are a subclass of endopeptidases which require activation by thiol reagents. A tumor cysteine proteinase which appears to be related to lysosomal cathepsin B has been implicated in the ability of tumor cells to invade the extracellular matrix and to metastasize to secondary sites. Lysosomal cathepsin B can degrade such components of the extracellular matrix as collagen, fibronectin and proteoglycans. Activity of this cathepsin B-like cysteine proteinase (CB) has been correlated with tumor malignancy in a number of tumor lines yet not in all tumor lines studied. CB activity in tumors seems to be associated with the viable tumor cells, probably with the plasma membrane of these tumor cells. CB activity has been measured in the sera, urine, ascites fluid and pancreatic fluid of tumor-bearing patients. CB is released from tumor explants and tumor cells in vitro as well as from normal subcutaneous tissue exposed to tumor-conditioned medium. Cathepsin B from normal tissues is rapidly inactivated above pH 7.0. Therefore, CB in tumor cell membranes or released from tumor cells (or from host cells in response to tumor cells) may not possess proteolytic activity at neutral pH and thus may not facilitate tumor cell invasion. However, CB exhibits enhanced stability at neutral or slightly alkaline pH's. There is not yet definitive proof that CB plays a role in tumor invasion and metastasis. There is, however, an increasing body of correlative evidence relating CB activity and tumor malignancy. This correlative evidence plus preliminary evidence that tumor CB can degrade components of the extracellular matrix in vitro suggests that CB may be one proteinase active in a proteolytic cascade resulting in tumor invasion and metastasis.
D000818:Animals; D002401:Cathepsin B; D002403:Cathepsins; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D003012:Microbial Collagenase / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology
D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D003012:Microbial Collagenase