The membrane proteases adams and hepsin are differentially expressed in renal cell carcinoma. Are they potential tumor markers?
OBJECTIVE
ADAMs (a disintegrin and metalloproteinases) as cell surface proteins with adhesion and protease activity, and hepsin as a transmembrane protease have important roles in many biological processes. We assessed the expression of various ADAMs and of hepsin in human renal cell carcinoma (RCC), and correlated expression with clinicopathological data.


METHODS
mRNA expression of ADAM-8, 17, 19, 28, TS1 and TS2, and of hepsin was investigated in paired tissue samples from cancerous and noncancerous parts of the kidneys of 27 patients with RCC who underwent tumor nephrectomy. Measurements were performed by quantitative real-time reverse transcriptase-polymerase chain reaction on a LightCycler instrument (Roche Applied Science, Mannheim, Germany). The data were related to housekeeping gene porphobilinogen deaminase mRNA.


RESULTS
All ADAMs except ADAM-TS1 were significantly higher but hepsin was less expressed (at least p <0.05) in cancerous vs matched noncancerous tissue. Expression was differentially related to tumor stage. ADAM-8 and ADAM-TS2 over expression as well as decreased hepsin expression were associated with shorter patient survival. The Cox proportional hazards regression model revealed that ADAM-TS2 was an independent prognostic factor for cancer related death. ADAM-8 was the best predictor of distant metastases.


CONCLUSIONS
The differential expression of hepsin and ADAMs suggests early and late involvement of membrane proteases in the development of RCC. Their association with the clinical outcome illustrates their potential usefulness as biomarkers for RCC.
Roemer
Andreas
A
Department of Urology, University Hospital Charité, Humboldt University, Berlin, Germany.
Schwettmann
Lutz
L
Jung
Monika
M
Stephan
Carsten
C
Roigas
Jan
J
Kristiansen
Glen
G
Loening
Stefan A
SA
Lichtinghagen
Ralf
R
Jung
Klaus
K
D051722:ADAM Proteins / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C055645:hepsin; D051722:ADAM Proteins