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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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Cancer cells spontaneously secrete microparticles in in vitro culture. Isolated membrane microparticles (MP) were identified by flow cytometry in a dot plot of forward light scattering (FSC) versus side light scattering (SSC). Size of MP was characterized using Fluorescent Microspheres of 0.5 and 1.0 μM. The majority population of cancer cells derived-MP is represented in black and it ranges between 0.5 μM (purple) and 1.0 μM (red) (a). 52.22% of the gated events of K562 cells derived-MP (b) and 50% of Lucena cells derived-MP were FITC-annexin V-positive (c).
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fig01: Cancer cells spontaneously secrete microparticles in in vitro culture. Isolated membrane microparticles (MP) were identified by flow cytometry in a dot plot of forward light scattering (FSC) versus side light scattering (SSC). Size of MP was characterized using Fluorescent Microspheres of 0.5 and 1.0 μM. The majority population of cancer cells derived-MP is represented in black and it ranges between 0.5 μM (purple) and 1.0 μM (red) (a). 52.22% of the gated events of K562 cells derived-MP (b) and 50% of Lucena cells derived-MP were FITC-annexin V-positive (c).

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).


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

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

Cancer cells spontaneously secrete microparticles in in vitro culture. Isolated membrane microparticles (MP) were identified by flow cytometry in a dot plot of forward light scattering (FSC) versus side light scattering (SSC). Size of MP was characterized using Fluorescent Microspheres of 0.5 and 1.0 μM. The majority population of cancer cells derived-MP is represented in black and it ranges between 0.5 μM (purple) and 1.0 μM (red) (a). 52.22% of the gated events of K562 cells derived-MP (b) and 50% of Lucena cells derived-MP were FITC-annexin V-positive (c).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Cancer cells spontaneously secrete microparticles in in vitro culture. Isolated membrane microparticles (MP) were identified by flow cytometry in a dot plot of forward light scattering (FSC) versus side light scattering (SSC). Size of MP was characterized using Fluorescent Microspheres of 0.5 and 1.0 μM. The majority population of cancer cells derived-MP is represented in black and it ranges between 0.5 μM (purple) and 1.0 μM (red) (a). 52.22% of the gated events of K562 cells derived-MP (b) and 50% of Lucena cells derived-MP were FITC-annexin V-positive (c).
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).

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