CATHEPSIN-D, CATHEPSIN-B AND CATHEPSIN-L IN BREAST-CARCINOMA AND IN TRANSFORMED HUMAN BREAST EPITHELIAL-CELLS (HBEC)

An increased expression of lysosomal enzymes, cathepsin (Cat) D, Cat B and Cat L, was observed in various human tumours and after in vitro c ell transformation. To establish possible cc-ordination in their expre ssion, all three cathepsins were determined in human breast tumours an d in transformed human breast epithelial cells (HBEC). In breast carci noma in = 120) all three cathepsins, determined immunochemically and b y enzymatic activity, were increased compar ed to normal breast tissue s. The activities correlated with the corresponding protein masses for Cat D (r = 0.77, p < 0.01), but not for Cat B and Cat L. Significant increase in Cat B activity was observed in stage II compared to stage I tumours, and Cat L activity in stage III compared to stage II tumour s, but no significant correlation of cathepsin protein with tumour sta ge (TNM) was established. No significant correlation between Cat D and the cysteine cathepsins B and L was observed. Similarly, Cat D, Cat B and Cat L levels did not correlate in the in vitro system, e.g, in th e five transformed HBEC, such as evolved after dimethylbenz(a)anthrace ne treatment and c-Has-ras oncogene transfection of diploid MCF-10F ce ll line (Calaf et al., 1993). Transformed cells showed increased ancho rage-independent growth and invasive capability (MCF-10 < MCF-10FTras < D3 < D3-1 < D3-1Tras). The intracellular level of Cat D was not rela ted to cell invasiveness, while total cellular Cat B and Cat L increas ed 13 fold and 4 fold, respectively, in the most invasive cell line, D 3-1Tras compared to MCF-10F. D3-1 Tras also secreted the largest amoun ts of Cat B. However, the relative secretion of cathepsin precursors w as not related to their intracellular amount and was not correlated wi th the invasive ability of HBEC.