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Trends in Molecular MedicineVolume 21, Issue 10, 1 October 2015, Article number 1063, Pages 595-608

Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles(Review)

  • aI3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
  • bCancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto, IPATIMUP, Porto, 4200-135, Portugal
  • cDepartment of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, 4050-313, Portugal
  • dDepartment of Pathology and Oncology, Faculty of Medicine of the University of Porto, Porto, 4200-319, Portugal

Abstract

Extracellular vesicles (EVs) are nanosized particles (100-1000. nm) enclosed by a phospholipid bilayer that have been described as important mediators of intercellular communication. The role of EVs in oncobiology has been extensively studied, including their contribution to the horizontal transfer of drug resistance from drug-resistant to drug-sensitive cancer cells. This review focuses on the EVs cargo responsible for this intercellular transfer of drug resistance; namely, drug-efflux pumps, miRNAs, long noncoding RNAs (lncRNAs), and other mediators. Additionally, the known molecular mechanisms and features of this transfer are discussed. This is an emerging area of research and we highlight topics that need to be further studied to fully understand and counteract the intercellular transfer of drug resistance mediated by EVs. EVs shed by drug-resistant (donor) cells contribute to the dissemination of CDR by transferring their cargo to drug-sensitive (recipient) cells.The cargo of the drug-resistant EVs may be selectively packaged and may include drug-efflux pumps, miRNAs, or lncRNAs.The drug-efflux pumps transferred by EVs to drug-sensitive cells are functional in the recipient cells.Drug-efflux pumps carried by EVs may be responsible for the sequestration of drugs in those EVs.EVs may protect miRNAs from the action of RNase. © 2015 Elsevier Ltd.

Indexed keywords

EMTREE drug terms:breast cancer resistance proteinlong untranslated RNAmicroRNAmultidrug resistance associated protein 1multidrug resistance protein
EMTREE medical terms:cancer resistancecell transferdrug resistanceexosomehumanmembrane microparticlenonhumanphenotyperegulatory mechanismReviewanimalcell communication
MeSH:AnimalsCell CommunicationDrug Resistance, NeoplasmExtracellular VesiclesHumans

Chemicals and CAS Registry Numbers:

multidrug resistance protein, 149200-37-3, 208997-77-7

Funding details

Funding sponsor Funding number Acronym
Programa Operacional Temático Factores de CompetitividadePEst-C/SAU/LA0003/2013’
Fundação para a Ciência e a Tecnologia
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  • 1

    IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. The work of the authors’ laboratory is funded by FEDER funds through the Operational Programme for Competitiveness Factors–COMPETE and national funds through the FCT under the project ‘PEst-C/SAU/LA0003/2013’. The authors also thank the FCT for grants to D.S. and R.T.L. (SFRH/BD/98054/2013 and SFRH/BPD/68787/2010, respectively) and the COST Action BM1202 European Network on Microvesicles and Exosomes in Health and Disease (ME-Had). Long noncoding RNAs (lncRNAs) a group of noncoding RNAs, more than 200 nucleotides long, that act as important transcriptional and post-transcriptional regulators. miRNAs small noncoding RNAs (18–24 nucleotides) that regulate gene expression. Alterations in miRNA profile have been associated with several malignancies such as cancer. Multidrug resistance (MDR) a phenomenon whereby cancer cells develop cross-resistance to various drugs following exposure to one drug that is structurally and functionally very dissimilar. Overexpression of ABC transporters is one of the major causes of the MDR phenotype observed in cancer cells. The main function of ABC transporters is the efflux of several amphipathic substrates, thereby protecting normal cells from toxic xenobiotics. In a drug resistance context, high levels of these efflux pumps, such as P-gp, ABCG2/breast cancer resistance protein (BRCP), or MRP1/ABCC1, results in the efflux of chemotherapeutic drugs from cancer cells culminating in intracellular sublethal concentrations of these compounds.

  • ISSN: 14714914
  • CODEN: TMMRC
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.molmed.2015.08.002
  • PubMed ID: 26432017
  • Document Type: Review
  • Publisher: Elsevier Ltd

  Vasconcelos, M.H.; I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
© Copyright 2015 Elsevier B.V., All rights reserved.

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