Procathepsin D Involvement in Chemoresistance of Cancer Cells

BACKGROUND: The role of pCD in cancer has been studied for a long time. We have focused on the hypothesis that increased expression and/or secretion of pCD in cancer cells causes increased chemoresistance to apoptosis inducing molecules. AIM: The aim was to evaluate the effects of pCD expression/release on chemoresistance. MATERIALS AND METHODS: We tested the LC(50) values for various transfectants of breast cancer cell line MDA-MB-231 as well as effects of exogenous additions of pCD, its mutants, pepstatine, antibodies, and Brefeldin on the resistance. RESULTS: We found that pCD levels can be correlated with chemoresistance, the pro-resistant activity seems to be localized outside the cells, proteolytic activity is not involved, and PI3-Akt signaling has an important role in antiapoptotic effects of pCD. CONCLUSION: We can conclude that overexpression of pCD has strong influence on increased resistance of tumor cells. This could, in fact, be an important contribution in the possible use of pCD level determination for prognostic and/or therapeutic purposes.