Expression of cathepsin B and cystatin C in human colorectal cancer

Cathepsin B is a matrix protease that map be associated with colorectal car cinoma invasion and progression. In this study, we investigated the localiz ation of cathepsin B in cancerous and noncancerous tissues of 80 patients w ith colorectal cancer including 25 cases with liver metastasis. In addition , the expression of cystatin C, one of several cathepsin B inhibitors,was c ompared with that of cathepsin B in the same samples to reveal one of the r egulation mechanisms of cathepsin B. The cancer cells in the advancing edge of the tumors often exhibited the strongest immunostaining of cathepsin B, and stromal cells and normal epithelial cells adjacent to the tumors were also positive for cathepsin B. The percentage of cathepsin B-positive cases was significantly larger in the group with liver metastases than in the gr oup without liver metastases. In the group without liver metastases, the ca ncer cells and stromal cells more frequently exhibited cathepsin B immunore activity in Dukes' A cases than in Dukes' B and C cases. In situ hybridizat ion and reverse transcription-polymerase chain reaction (RT-PCR) confirmed cathepsin B synthesis in the cancer and proximal epithelial cells. There wa s an average 3.7-fold increase in cathepsin B mRNA levels in the cancerous tissues compared with that of noncancerous tissues, and Dukes' A tumors exh ibited the highest expression level. Conversely, cystatin C mRNA levels wer e similar in all samples, and tended to show an inverse correlation with th e cathepsin B levels. In conclusion, cathepsin B expression by human colore ctal cancers and surrounding noncancerous cell components may contribute to both local invasion at the early stage and remote metastasis without influ ence of cystatin C. Copyright (C) 1999 by W.B. Saunders Company.