Cell membrane expression of HSP70 in cisplatin resistant tumour cells may be targeted through the co-localized glycosphingolipid Gb3
(English)Manuscript (preprint) (Other academic)
Globotriaosylceramide (Gb3) and heat-shock protein 70 (HSP70) are often co-localized on the cell surface of tumours and facilitates metastasis and cisplatin resistance. We hypothesized that targeting Gb3 could also inhibit HSP70 expression in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM).
Gb3 and HSP70 were co-localized on the cell surface. The glucosylceramide synthaseinhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP), Gb3 synthase siRNA and VT-1 reduced Gb3 and HSP70 expression, while HSP90-inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) increased Gb3 and HSP70. The combination of 17-AAG and VT-1 had a synergistic cytotoxic effect.
Cell membrane HSP70 expression in cisplatin-resistant tumour cells may be targeted through co-localized Gb3.
Globotriaosylceramide, heat shock protein 70, cisplatin, verotoxin-1, glycosphingolipid, glucosylceramide synthase
Cell and Molecular Biology
Research subject cellforskning; Medical Cell Biology; Oncology
IdentifiersURN: urn:nbn:se:umu:diva-119786OAI: oai:DiVA.org:umu-119786DiVA: diva2:923683
FunderSwedish Cancer Society, CAN 2011/599