Proenzyme to urokinase-type plasminogen activator in human colon cancer: in vitro inhibition by monocyte minactivin after proteolytic activation.
Marked increases of plasminogen activator activity were observed in human colon cancer tissue, compared to corresponding normal tissues. This increase was attributable to urokinase-type activator (HPA52), with no increase evident in the level of the tissue-type plasminogen activator (HPA66). Human monocyte minactivin specifically inhibited HPA52 activity in cancer tissue homogenates and in colon cancer cell supernatants, an effect that was greatly enhanced by preincubation with plasminogen, indicating that the predominant form of HPA52 in tissue and the form that is secreted in vitro is the proenzyme. Inactivation of HPA52 by minactivin was shown to be dependent on proteolytic activation of HPA52 proenzyme. Utilization of HPA52 activity by tumors in vivo could therefore be dependent upon a protease, such as plasmin, to generate the extracellular proteolytic activity necessary to digest the intercellular matrix and permit invasion of normal tissue structures by colon cancer cells.
Stephens
R W
RW
Department of Medicine and Clinical Science, John Curtin School of Medical Research, Australian National University.
Fordham
C J
CJ
Doe
W F
WF
D000328:Adult; D000368:Aged; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors*; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015849:Plasminogen Inactivators; D014407:Tumor Cells, Cultured / Q000201:enzymology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D004792:Enzyme Precursors; D015849:Plasminogen Inactivators; C039812:minactivin; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator