Matrix metalloproteinase activity in urine of patients with renal cell carcinoma leads to degradation of extracellular matrix proteins: possible use as a screening assay.
OBJECTIVE
Localized renal cell carcinoma is usually curable by nephrectomy. However, a large fraction of patients already present with metastatic disease, which results in a poor outcome. Currently no clinically relevant screening assay is available to detect early stage renal cell carcinoma. We investigated whether urinary extracellular matrix (ECM) proteins and/or matrix metalloproteinase (MMP) activity may be valuable as a noninvasive indicator of early stage renal cell carcinoma.


METHODS
Urine specimens from preoperative patients with renal cell carcinoma and healthy controls were collected. The urinary excretion of the ECM proteins collagen IV, laminin and fibronectin was investigated by immunoblotting. MMP activity was assessed by gelatin zymography and by a fluorescence based microtiter plate activity assay.


RESULTS
The full-length forms of all 3 ECM proteins investigated were significantly decreased or absent in renal cell carcinoma urine. Based on criteria established in this study this finding would lead to the correct detection of 95% of patients with renal cell carcinoma (21 of 22) with a false-positive rate of 4.5% (1 of 22 controls). All 11 nonmetastatic cases of the lowest clinical stage (T1N0M0) were correctly identified. The absence of urinary ECM proteins was due to significantly increased urinary MMP activity.


CONCLUSIONS
Analysis of decreased urinary ECM proteins and analysis of increased MMP activity may have value for the development of a sensitive, high throughput molecular screening assay to detect early stage renal cell carcinoma.
Sherief
Mahmoud H
MH
Department of Cell Biology, Lerner Research Institue, The Cleveland Clinic, Ohio, USA.
Low
Seng Hui
SH
Miura
Masumi
M
Kudo
Noriko
N
Novick
Andrew C
AC
Weimbs
Thomas
T
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D024141:Collagen Type IV / Q000652:urine; D016326:Extracellular Matrix Proteins / Q000652:urine*; D005260:Female; D005353:Fibronectins / Q000652:urine; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D007797:Laminin / Q000652:urine; D008297:Male; D008403:Mass Screening; D020782:Matrix Metalloproteinases / Q000652:urine*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012016:Reference Values
D014408:Biomarkers, Tumor; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D020782:Matrix Metalloproteinases