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

Paloma Silva de Souza1, André L S Cruz, João P B Viola

  • 1Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

Cancer Science
|December 3, 2014
PubMed

Insights

Membrane microparticles (MP) transfer multidrug resistance (MDR) proteins to sensitive cancer cells. This transfer induces MDR, conferring resistance to chemotherapy agents through multiple mechanisms.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Multidrug resistance (MDR) is a complex phenomenon limiting chemotherapy efficacy.
  • Key MDR mechanisms include P-glycoprotein (Pgp/ABCB1) efflux, inhibitor of apoptosis proteins (IAP) evasion, and oncogenic pathway activation.
  • MDR-associated molecules are found in membrane microparticles (MP).

Purpose of the Study:

  • To investigate the role of membrane microparticles (MP) in mediating multidrug resistance (MDR) transfer between cancer cells.
  • To determine if MP can induce a multifactorial MDR phenotype in sensitive recipient cells.

Main Methods:

  • Co-culturing of MP derived from MDR-positive cells with sensitive recipient cancer cells.
  • Analysis of Pgp, IAP proteins, and mRNA levels in recipient cells.
  • Assessment of microRNA transfer, NFκB, and Yb-1 activation.

Main Results:

  • Sensitive cancer cells exposed to MP accumulated Pgp and IAP proteins and mRNA.
  • MP facilitated the transfer of microRNAs into recipient cells.
  • MP induced activation of NFκB and Yb-1 signaling pathways in sensitive cells.

Conclusions:

  • Membrane microparticles (MP) play a significant role in the intercellular transfer of multidrug resistance (MDR).
  • MP can induce a multifactorial MDR phenotype in sensitive cancer cells, enhancing their survival and resistance.
  • Targeting MP-mediated transfer could be a novel strategy to overcome MDR in cancer therapy.
Keywords:
Inhibitors of apoptosis proteinsNFκBP-glycoproteinmicroparticlesmultidrug resistance

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