A cleaved form of the receptor for urokinase-type plasminogen activator in invasive transplanted human and murine tumors.
It was recently found that urokinase-type plasminogen activator (uPA) is involved in the cleavage of its receptor (uPAR) on cultured cells, thereby releasing one of the receptor's 3 domains (the ligand binding domain I) and leaving the 2 others [uPAR(2 + 3)] anchored to the cell surface. With monoclonal antibodies (MAbs) we have now identified human uPAR(2 + 3) in lysates of invasive human MDA-MB-231 mammary carcinomas xenografted into nude mice. The production of peptide antibodies recognizing different domains of murine uPAR made it possible to identify a similar cleaved form of uPAR, murine uPAR(2 + 3), in extracts of primary Lewis lung carcinomas. Cleavage of uPAR also occurs in cultured MDA-MB-231 cells and Lewis lung carcinoma cells. This cleavage is inhibited by anticatalytic antibodies to either human or murine uPA, respectively, indicating that it is catalyzed by either uPA or plasmin generated by uPA. The amount of uPAR(2 + 3) may therefore be directly related to the activity of the uPA system and it is possible that the level of uPAR(2 + 3) in cancer tissue may prove to be a stronger prognostic parameter than the levels of either full-length uPAR or UPA.
Solberg
H
H
Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Rømer
J
J
Brünner
N
N
Holm
A
A
Sidenius
N
N
Danø
K
K
Høyer-Hansen
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure*; D002384:Catalysis; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure*; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator