Increase of a urokinase receptor-related low-molecular-weight molecule in colorectal adenocarcinomas.
Proteolytic activity is important for tumor growth and metastasis. Plasminogen and urokinase-type plasminogen activator (u-PA) constitute one of the most extensively studied proteolytic systems believed to participate in these processes. u-PA cleaves plasminogen to plasmin, which in turn degrades surrounding extracellular matrix and allows tumor cells to migrate to other areas. The specific receptor for u-PA (u-PAR) has also been implicated as an essential modulator in this pathway. Eleven paired samples of colorectal cancers and normal mucosal tissues from the same patients were removed at surgery. The tissues were homogenized and the supernatants assayed for u-PAR immunoreactivity, u-PAR antigen concentration, u-PAR binding activity and u-PA activity. Immunoblot analysis showed that a major u-PAR species of approximately 55 kDa was present in all tissues. In addition, a protein band of approximately 41 kDa, which crossreacted with anti-u-PAR antibodies, was also found in the tumors. This protein band was either absent, or present in relatively small amounts in the normal colorectal tissues. Cross-linking experiments showed that the approximately 55 kDa band only, and not the approximately 41 kDa band, was able to bind either single chain urokinase-type plasminogen activator (scu-PA) or the amino terminal fragment of urokinase (ATF). The tumor samples also exhibited highly elevated u-PA activity and u-PAR antigen relative to the corresponding normal tissues. Elevated u-PA activity appeared to correlate with elevated u-PAR antigen in colorectal cancers, but not in the normal tissues. These increases were also associated with increase of the u-PAR-related, low-molecular-weight protein in the tumor samples. The measurement of u-PAR and the u-PAR-related protein, in addition to u-PA activity, could have diagnostic or prognostic value in this type of cancer.
Lau
H K
HK
Division of Hematology and Oncology, St Michael's Hospital, Toronto, Ontario, Canada.
Kim
M
M
Koo
J
J
Chiu
B
B
Murray
D
D
D000230:Adenocarcinoma / Q000378:metabolism*; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism*; D006801:Humans; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator