CHLOROQUINE ALTERS EXPRESSION AND DISTRIBUTION OF CATION-DEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR OF BREAST CANCER CELLS

PEREYRA L; PERALTA S; CUNIETTI M; VARGAS-ROIG L; SOSA M; CARVELLI L,

Congreso; XXXVII Reunión Anual de la Sociedad de Biología de Cuyo; 2019

Sociedad de Biología de Cuyo

Breast cancer is one of the most important causes of morbidity and mortality worldwide. Several tumoral cells have increased theirlysosomal biogenesis in response to metabolic alterations, which also has an impact on the integrity and/or lysosomal functionality,showing increased levels of lysosomal proteases, such as cathepsin D (CatD). CatD was reported to induce apoptosis when it isreleased into the cytoplasm. Since the lysosomes could play a role either as initiators or executors of apoptotic processes when themembrane integrity is altered, this organelle could be taken as a potential therapeutic target against tumors. Lysosomal proteases aredelivered by mannose-6-phosphate receptors (cation dependent, CD-MPR, and independent-, CI-MPR) from the trans-Golgi to lateendosomes, where enzyme-receptor complexes are dissociated, and the receptor recycled. Chloroquine (CQ) is a lysosomotropicagent that prevents endosomal acidification. It accumulates inside the acidic compartments and it is used as a potent adjuvant whencombined with antitumoral drugs. The aim of this study was to evaluate the effect of CQ on the lysosomal protease endocyticpathway through the CD-MPR behavior in breast cancer cells. Tumorigenic mammary cell line MCF-7 was incubated with CQ for12 h. Cultures were subjected to immunoblot analysis and IFI. We observed an increased expression of CD-MPR by the treatment.Moreover, the receptor is redistributed from a perinuclear region to a punctuated cytoplasmic detection. In addition, the mature CatDform was decreased by the treatment. Our results suggest that CD-MPR-containing compartments are affected by CQ, possiblyleading to impeded CatD trafficking and processing.