Secreted cellular prion protein binds doxorubicin and correlates with anthracycline resistance in breast cancer.

ABSTRACT: Anthracyclines are amongst the most effective chemotherapeutics ever developed, but they produce grueling side-effects, serious adverse events and resistance often develops over time. We found that these compounds can be sequestered by secreted cellular Prion protein (PrPC), blocking their cytotoxic activity. This effect was dose-dependent using either cell line-conditioned medium or human serum as a source of PrPC. Genetic depletion of PrPC or inhibition of binding via chelation of ionic copper prevented the interaction and restored cytotoxic activity. This was more pronounced for doxorubicin than its epimer, epirubicin. Investigating the relevance to breast cancer management, we found that the levels of PRNP transcript in pre-treatment tumor biopsies stratified relapse-free survival afte

SUBMITTER: Wiegmans AP 

PROVIDER: S-EPMC6483007 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature