Cathepsins D, B, and L in malignant human lung tissue.
The levels of cathepsins in malignant and surrounding nonmalignant lung tissue were determined in 17 non-small cell lung cancer specimens. Cathepsin (Cat) D activity was assayed using hemoglobin, whereas Cat B and Cat L activities were assayed using fluorimetric substrates, benzoylcarbonyl-Ala-Arg-Arg-7-amino-4-methylcoumarine and benzoylcarbonyl-Phe-Arg-7-amino-4-methylcoumarine, respectively. Cat protein concentrations were determined using ELISAs. In malignant tissues, the activities of Cat B and Cat L were significantly higher than the activities in nonmalignant tissues (P < 0.0012 and P < 0.0003, respectively), whereas Cat D concentration was not. There was also a 5.6-fold increase in median Cat B protein (P < 0.054) and a 2.2-fold increase in Cat L protein (P < 0.069). By contrast, the aspartic proteinase, Cat D protein, was not significantly increased in tumors versus control lung tissues. Moderate but significant correlation (r = 0.5, P < 0.045) between Cat B and Cat L expression was observed, but neither correlated with Cat D. The relative increase in median Cat L activity (P < 0.037) and protein (P < 0.0005) was greater in poorly differentiated tumors than in moderate ones. Cat L activity (P < 0.003) and protein (P < 0. 005) increases were higher in adenocarcinoma than in squamous cell carcinoma. We conclude that in lung cancers the three lysosomal enzymes are regulated in a noncoordinate manner and that there is specific induction of cysteine cathepsins. Whether Cat B and/or Cat L would be of diagnostic and/or prognostic value requires further study in a larger patient population.
Ledakis
P
P
Department of Pathology and Laboratory Medicine and Cancer Center, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, USA.
Tester
W T
WT
Rosenberg
N
N
Romero-Fischmann
D
D
Daskal
I
I
Lah
T T
TT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002401:Cathepsin B / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005260:Female; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight
D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; D002402:Cathepsin D