Expression of Cathepsin B and L antigen and activity is associated with early colorectal cancer progression.
Cathepsin B and Cathepsin L are cysteine proteases important in the process of invasion and metastasis. The aim of our study was to assay antigen and activity levels of these enzymes and to correlate these with established clinical and pathological prognostic parameters including patient survival. 99 patients undergoing operations for colorectal cancer were included in this study. We quantitated cathepsin B and L levels in matched normal mucosa and cancer samples using an enzyme-linked immunosorbent assay (ELISA) and specific activity assays and expressed the results as tumour/normal ratios. Significant correlations were found between tumour/normal cathepsin B and L antigen and activity ratios. Cathepsin B and L tumour/normal activity ratios were greater than 1 in early stage disease and there were gradual reductions in cathepsin B (P = 0.02) and L (P = 0.03) activity ratios with advancing tumour stage. Survival of patients with potentially curative disease was inversely related to both cathepsin B (P = 0.007) and L (P = 0.001) activity ratio, in addition to cathepsin L antigen ratio (P = 0.008). Our findings suggest that cysteine proteases play an important role in colorectal cancer progression.
Troy
A M
AM
Centre for Colorectal Disease, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Sheahan
K
K
Mulcahy
H E
HE
Duffy
M J
MJ
Hyland
J M P
JM
O'Donoghue
D P
DP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
D009363:Neoplasm Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L