EXTRACELLULAR VESICLES TRANSFER RESISTANCE TO VINCRISTINE IN SONIC HEDGEHOG MEDULLOBLASTOMA

Abstract AIMS • To determine the expression patterns of specific ATP-binding cassette (ABC) transporters in medulloblastoma assess whether ABC play a role acquired drug resistance SHH using drug-tolerant cell line models extracellular vesicles transfer drug-tolerance and mechanism by which they do this METHOD Drug-tolerant lines were generated continuous culture drug-containing medium. trans- porter gene protein was assessed via qPCR western blot. EVs isolated from EV-depleted medium size-exclusion chromatography. Nanoparticle tracking analysis used to quantify deter- mine size. Cytotoxicity EV-mediated presence or absence an transporter inhibitor. RNA sequencing matched vehicle tolerant carried out. RESULTS Analysis revealed significant increases across subgroups. ABCB1 significantly higher sonic- hedgehog (SHH) inhibition abolished vincristine. assays on sensitive cells, after pre-treatment with EVs, showed increase vincristine resistance, implicating resistance. CONCLUSIONS Data date supports hypothesis that multidrug carrying may their resistant phenotype surrounding cells medulloblastoma. We are currently testing inhibitors knockout lines, addition sequencing, hopes providing new therapeutic targets patients