Microparticles mediate MRP1 intercellular transfer and the re-templating of intrinsic resistance pathways.

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Journal Article
Pharmacological Research, 2013, 76 pp. 77 - 83
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Multidrug resistance (MDR) is a major impediment to the overall success of chemotherapy in clin-ical oncology. MDR has been primarily attributed by the ATP-dependent transmembrane proteins,P-glycoprotein (P-gp, ABCB1) and Multidrug Resistance-Associated Protein 1 (MRP1, ABCC1). These pro-teins maintain sublethal concentrations of intracellular chemotherapeutics by virtue of their drug effluxcapacity. In this study, we report the acquisition and dissemination of functional MRP1 via microparticle(MP) mediated intercellular transfer. After we showed the transfer and functionality of P-gp in drug sen-sitive recipient cells, we report the transfer and time-dependent functionality of MRP1 in drug sensitiveleukaemia cells following exposure to MPs shed by MRP1-overexpressing MDR cells. We also demonstratea remarkable capacity for MPs shed from cells with a P-gp dominant resistance profile to re-template apre-existing MRP1 dominant profile in recipient cells. These findings have significance in understandingthe molecular basis for tumour dominant phenotypes and introduce potential new strategies and targetsfor the acquisition of MDR and other deleterious traits.
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