The role of peptidases in cancer of the rectum and sigmoid colon

Abstract

Abstract Increased levels of peptidases are found in some human carcinomas and may be related to invasive potential. We therefore measured the activity of four peptidases in 50 specimens of tumour and normal colonic wall from patients with a rectal or sigmoid carcinoma, and correlated this with the stage, differentiation, fixity of the tumour and presence of venous invasion, determined histologically. Since acute phase reactant proteins (APRP) may inhibit these proteolytic enzymes we have also measured serum levels of two relevant APRPs, α1 acid glycoprotein (AGP) and C-reactive protein (CRP) pre-operatively. Activity of cathepsin B, cathepsin H and collagenase-like peptidase (CLP) was determined fluorimetrically and collagenase photometrically. Significantly elevated activity of cathepsin B, CLP and collagenase was found in tumour compared with normal colonic wall (median values: (nmol (mg protein)−1 min−1) Cat B 0.71 and 0.42 (P<0.001), CLP 25.24 and 12.25 (P<0.001) and collagenase 0.49 and 0.31 (P<0.001)). There was no correlation between the activity of these enzymes expressed as a ratio of tumour/colonic wall, and differentiation or Dukes' stage of the tumour. However, there was significant elevation of activity of cathepsin B in tumours with local spread (n = 13) compared with those with no spread (n = 37) (median values 2.76 and 1.36 respectively (P<0.001)) and also in tumour with venous invasion (n = 24) compared with tumours without (n = 26) (median values 1.82 and 1.18 respectively (P<0.01)). Pre-operative serum levels of CRP were inversely correlated with the activity of CLP and cathepsin H and collagenase in the tumours (rs = 0.332, 0.359 (P<0.05) and 0.302 (P = 0.05) respectively). Thus certain peptidases are raised in rectal and sigmoid tumours. Activity of cathepsin B appears related to local tumour invasion. APRP may have a role in inhibiting the activity of these enzymes. These findings may have therapeutic implications.