Proteaze in proteazni inhibitorji v napredovanju raka: možna uporaba v prognozi, preventivi in antimetastatski terapiji (Slovene)

Proteinases play an important role in distinct steps during tumor progression and most likely contribute in cascade proteolytic events which help tumor cells during the three-step process of invasion. Presumably, lysosomal proteinases, cathepsins, are involved in the cascade. In this study, cathepsins B and L and their endogenous inhibitors, stefins A and B are evaluated in: 1) Breast carcinoma at various stages of progression. We compare the enzyme activities and protein content of these biological markers with other proteolytic systems, with clinical and histo-pathological properties of breast tumors and with the patients survival- (2) Brain tumors, where we elucidate gene regulation of this proteolytic system: we will measure and compare the levels (mRNA, protein and activity) of cathepsins and stefins in benign and malignant tumors. (3) Brain and breast tumor cell lines with different in vitro invasive potential. In the in vitro invasion assay, which we developed, we are evaluating the effect of various proteolytic enzymes on cell adhesion, chemotaxis and chemo-invasion. The results of these studies will elucidate: (a) the role and possible correlation of cysteine cathepsins with the tumor cell invasivness, (b) possible application of proteases and inhibitors in the prognosis of breast cancer and possible application of protease inhibitors in preventing invasion of metastatic cells and consequently their use in cancer therapy.