Expression of cathepsin B is related to tumorigenicity of breast cancer cell lines

Abstract

Background. The lysosomal cysteine proteases cathepsins B (CatB) and L (CatL) and their endogenous inhibitors, stefins A (StA) and B (StB), are widely thought to be involved in the progression of human breast carcinoma. Previously we showed that, in model breast carcinoma cell lines, the reported tumorigenicity was not directly related to their in vitro invasive potential. However, CatL expression was positively related to the invasiveness of the cells and inversely related to the levels of StA. Here we challenge the hypothesis that imbalance between CatB and the two stefins is associated either with the invasiveness or the reported tumorigenicity of the panel of selected breast carcinoma cells.

Results. We investigated levels of mRNA, protein and activity for CatB in the panel of human breast carcinoma cell lines whose tumorigenicity in vivo increased in the order MCF-7 YXC MDA-MB468 YXC MDAMB231 YXC MDA-MB435, the most invasive being MDA-231. Levels of expression of mRNA, protein and activity for CatB were highly correlated and increased progressively with cell tumorigenicity. The ratio of CatB to stefins was shifted in favour of CatB in the more tumorigenic cell lines.

Conclusions. Since CatL has been shown previously to be associated with invasive potential and, in this study, CatB expression was found positively associated with the tumorigenicity of the same breast carcinoma cell lines, the two cathepsins in these cells do not appear to be regulated in a coordinated manner. CatB expression and the ratio between CatB and stefins increased progressively with tumorigenicity of the cells and suggests a similar situation in human tumours in vivo.