Increased mRNA expression of ADAMs in renal cell carcinoma and their association with clinical outcome.
ADAMs (a disintegrin and metalloproteinase) are cell-surface proteins with adhesion and protease activity which play important roles in many biological processes. Little is known about their role in cancer. The aim of the study was to assess the quantitative expression of the ADAMs in human renal cell carcinoma (RCC) and to associate expression levels with clinicopathological data. We investigated the mRNA expression of ADAM-8, -17, -19, -28, ADAM-TS1, and ADAM-TS2 in paired tissue samples from cancerous and non-cancerous parts of the kidneys of 27 patients with RCC who underwent tumour nephrectomy. Measurements were performed by means of the quantitative real-time RT-PCR on a LightCycler instrument. ADAM-8, -17, and -19 were significantly higher expressed (p<0.05 at least) in cancerous compared with the matched non-cancerous tissue in pT1 and > or =pT2 tumours, ADAM-28 and ADAM-TS2 only in pT1 tumours, and ADAM-TS1 was not differently expressed. All ADAMs except ADAM-TS1 showed an increase of expression in the non-cancerous tissue with rising pT stage suggesting an early involvement of ADAMs in the development of RCC. The expression of ADAM-8 was related to a shorter survival of patients and was the best predictor of distant metastases. Our results indicate a potential role for ADAMs in RCC and that the overexpression might be a useful predictive tool.
Roemer
Andreas
A
Department of Urology, University Hospital Charité, Humboldt University, Schumannstrasse 20/21, D-10098 Berlin, Germany.
Schwettmann
Lutz
L
Jung
Monika
M
Roigas
Jan
J
Kristiansen
Glen
G
Schnorr
Dietmar
D
Loening
Stefan A
SA
Jung
Klaus
K
Lichtinghagen
Ralf
R
D000368:Aged; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017931:DNA Primers; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics*; D016019:Survival Analysis; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics*; D016896:Treatment Outcome
D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger; D008666:Metalloendopeptidases