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.