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: Our results showed that MDR cell-derived MP contained miR-27a, miR-451 and miR-21 from donor cells (Fig.2c). Indeed, we evaluated the transfer of miR-27a, miR-451 and miR-21 from MDR cell-derived MP to recipient cells. Our results showed that miR-27a and miR-451 were upregulated in A549 and MCF7 recipient cells after co-culturing. In addition, MCF7 cells showed an increase in oncogenic miR-21 expression levels after co-culturing (Fig.6a,b). These data suggest that miR-27a and miR-451 may contribute to the positive regulation of intrinsic ABCB1 mRNA expression in recipient cells and that miR-21 may contribute to malignant tumor potential. In addition, we analyzed the Akt activation in both recipient cells, due to the fact that this kinase can be related to NFκB activation via miR-21.25 After co-culturing, MCF7 showed an increase in phosphorylated Akt protein (Fig.6c)
Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.