Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type.
Bottom Line: By co-culturing MP derived from MDR-positive cells with recipient cells, we showed that sensitive cells accumulated Pgp, IAP proteins and mRNA.In addition, MP promoted microRNA transfer and NFκB and Yb-1 activation.Therefore, our results indicate that MP can induce a multifactorial phenotype in sensitive cancer cells.
Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.Show MeSH
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Mentions: Recently, MP from MDR acute lymphoblastic leukemia (ALL) cells have been reported to mediate the transfer of Pgp to drug sensitive ALL cells.12 Based on this information, MP derived from CML sensitive cells and a drug-resistant variant were purified and analyzed as described in the Material and Methods. Our results demonstrated that both sensitive and drug-resistant CML cells were able to spontaneously release MP into in vitro culture conditions, representing 52.22% and 50%, respectively, of the FITC-annexin V positive population after phosphatidylserine exposure (Fig.1). We confirmed that MDR cell-derived MP could transport Pgp onto the cell surface. Approximately 22% of the MP-gated population was positive for Pgp. However, MP derived from sensitive cells did not contain Pgp (Suppl. Fig. S1).
Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.