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Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type.

de Souza PS, Cruz AL, Viola JP, Maia RC - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

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Changes in microRNA expression profile and activation of Akt pathway in multidrug resistant (MDR)-negative recipient cells after co-culturing with isolated membrane microparticles (MP). miR-27a, miR-451 and miR-21 were upregulated in MDR-negative cells after co-culturing with MDR-positive MP. A549 recipient cells showed an increase of miR-27a and mir-451 expression levels after co-culturing with MDR-positive MP (a). MCF7 recipient cells showed upregulation of miR-27a, miR-451 and miR-21 expression levels after co-culturing with MDR-positive MP (b). MCF7 recipient cells showed activation of phosphorylated Akt (pAkt) (c). Each bar represents the mean ± SD of triplicate experiments. *P < 0.05, **P < 0.01.
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fig06: Changes in microRNA expression profile and activation of Akt pathway in multidrug resistant (MDR)-negative recipient cells after co-culturing with isolated membrane microparticles (MP). miR-27a, miR-451 and miR-21 were upregulated in MDR-negative cells after co-culturing with MDR-positive MP. A549 recipient cells showed an increase of miR-27a and mir-451 expression levels after co-culturing with MDR-positive MP (a). MCF7 recipient cells showed upregulation of miR-27a, miR-451 and miR-21 expression levels after co-culturing with MDR-positive MP (b). MCF7 recipient cells showed activation of phosphorylated Akt (pAkt) (c). Each bar represents the mean ± SD of triplicate experiments. *P < 0.05, **P < 0.01.

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)


Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type.

de Souza PS, Cruz AL, Viola JP, Maia RC - Cancer Sci. (2014)

Changes in microRNA expression profile and activation of Akt pathway in multidrug resistant (MDR)-negative recipient cells after co-culturing with isolated membrane microparticles (MP). miR-27a, miR-451 and miR-21 were upregulated in MDR-negative cells after co-culturing with MDR-positive MP. A549 recipient cells showed an increase of miR-27a and mir-451 expression levels after co-culturing with MDR-positive MP (a). MCF7 recipient cells showed upregulation of miR-27a, miR-451 and miR-21 expression levels after co-culturing with MDR-positive MP (b). MCF7 recipient cells showed activation of phosphorylated Akt (pAkt) (c). Each bar represents the mean ± SD of triplicate experiments. *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317771&req=5

fig06: Changes in microRNA expression profile and activation of Akt pathway in multidrug resistant (MDR)-negative recipient cells after co-culturing with isolated membrane microparticles (MP). miR-27a, miR-451 and miR-21 were upregulated in MDR-negative cells after co-culturing with MDR-positive MP. A549 recipient cells showed an increase of miR-27a and mir-451 expression levels after co-culturing with MDR-positive MP (a). MCF7 recipient cells showed upregulation of miR-27a, miR-451 and miR-21 expression levels after co-culturing with MDR-positive MP (b). MCF7 recipient cells showed activation of phosphorylated Akt (pAkt) (c). Each bar represents the mean ± SD of triplicate experiments. *P < 0.05, **P < 0.01.
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)

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.

View Article: PubMed Central - PubMed

Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

Show MeSH
Related in: MedlinePlus