Cathepsin B and tumor-associated laminin expression in the progression of colorectal adenoma to carcinoma

Ashraf Khan, University of Massachusetts Medical School
Murli Krishna
Stephen P. Baker, University of Massachusetts Medical School
Barbara F. Banner, University of Massachusetts Medical School

Abstract

Cathepsin B is a lysosomal cysteine proteinase associated with degradation of laminin. It is increased in colorectal carcinoma (CA). Laminin is a major component of basement membrane involved in cell-matrix interactions and tumor progression. The aim of this study was to correlate cathepsin B and tumor-associated laminin in colorectal adenomas (ADs) with increasing grades of dysplasia and in invasive CAs. Forty-five ADs (8 tubular, 16 tubulovillous, 21 villous), 13 adenomas with high-grade dysplasia/carcinoma in situ (AHDs), and 17 invasive CAs were immunostained with polyclonal antibodies to cathepsin B and laminin. Statistical analysis was performed using exact linear by linear association test and Spearman rank correlation coefficient. Cathepsin B-positive tumor cells were seen in 30 (67%) ADs, 13 (100%) AHDs, and 17 (100%) CAs. The grade of cathepsin B staining was significantly increased in AHDs and CAs, compared with ADs (P < .0001). Laminin was continuous in all of the ADs and discontinuous or fragmented in the AHDs and CAs (P < .0001). The degree of cathepsin B staining in tumor cells also correlated with breakdown of laminin. Increased cathepsin B expression and decrease in tumor-associated laminin might suggest a mechanism for progression of ADs to CAs.