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 cell transformation. To establish possible cc-ordination in their expression, all three cathepsins were determined in human breast tumours and in transformed human breast epithelial cells (HBEC). In breast carcinoma in = 120) all three cathepsins, determined immunochemically and by enzymatic activity, were increased compar ed to normal breast tissues. 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 tumours, but no significant correlation of cathepsin protein with tumour stage (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 the five transformed HBEC, such as evolved after dimethylbenz(a)anthracene treatment and c-Has-ras oncogene transfection of diploid MCF-10F cell line (Calaf et al., 1993). Transformed cells showed increased anchorage-independent growth and invasive capability (MCF-10 < MCF-10FTras < D3 < D3-1 < D3-1Tras). The intracellular level of Cat D was not related to cell invasiveness, while total cellular Cat B and Cat L increased 13 fold and 4 fold, respectively, in the most invasive cell line, D3-1Tras compared to MCF-10F. D3-1 Tras also secreted the largest amounts of Cat B. However, the relative secretion of cathepsin precursors was not related to their intracellular amount and was not correlated with the invasive ability of HBEC.