Skip Main Navigation Links Jump to Footer

Scopus Preview

Biochimica et Biophysica Acta - General SubjectsVolume 1860, Issue 3, March 2016, Pages 618-627

Multidrug resistant tumour cells shed more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart cells(Article)

  • Lopes-Rodrigues, V.,
  • Di Luca, A.,
  • Sousa, D.,
  • Seca, H.,
  • Meleady, P.,
  • Henry, M.,
  • Lima, R.T.,
  • O'Connor, R.,
  • Vasconcelos, M.H.
  • View Correspondence (jump link)
  • ai3S - Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Portugal
  • bCancer Drug Resistance Group, IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto, 4200-465, Portugal
  • cICBAS-UP, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, 4099-003, Portugal
  • dNICB - National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
  • eDepartment of Biological Sciences, FFUP, Faculty of Pharmacy, University of Porto, Porto, 4050-313, Portugal
  • fDepartment of Pathology and Oncology, FMUP - Faculty of Medicine of the University of Porto, Porto, 4200-319, Portugal

Abstract

Background Multidrug resistance (MDR) is a serious impediment to cancer treatment, with overexpression of drug efflux pumps such as P-glycoprotein (P-gp) playing a significant role. In spite of being a major clinical challenge, to date there is no simple, minimally invasive and clinically validated method for diagnosis of the MDR phenotype using non-tumour biological samples. Recently, P-gp has been found in extracellular vesicles (EVs) shed by MDR cancer cells. This study aimed to compare the EVs shed by MDR cells and their drug-sensitive cellular counterparts, in order to identify biomarkers of MDR. Methods Two pairs of MDR and drug-sensitive counterpart tumour cell lines were studied as models. EVs were characterized in terms of size and molecular markers and their protein content was investigated by proteomic analysis and Western blot. Results We found that MDR cells produced more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart. EVs from MDR cells contained P-gp and presented a different content of proteins known to be involved in the biogenesis of EVs, particularly in the biogenesis of exosomes. Conclusions The determination of the size and of this particular protein content of EVs shed by tumour cells may allow the development of a minimally-invasive simple method of detecting and predicting MDR. General significance This work describes for the first time that cancer multidrug resistant cells shed more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart cells, carrying a specific content of proteins involved in EV biogenesis that could be further studied as biomarkers of MDR. © 2015 Elsevier B.V. All rights reserved.

Author keywords

Extracellular vesiclesMultidrug resistanceTumour cells

Indexed keywords

EMTREE drug terms:biological markerCD63 antigenCD83 antigenclathrin LCBdoxorubicinetoposideheat shock protein 70multidrug resistance proteinprotein Alixprotein CHMP4Bsyntenin 1tumor susceptibility gene 101 proteinunclassified drug
EMTREE medical terms:Articlebiogenesiscancer cell linecell isolationcontrolled studydrug sensitivityexosomehumanhuman cellK562 cell lineliquid chromatographymembrane microparticlemolecular sizemultidrug resistanceNCI H460 cell linephoton correlation spectroscopypriority journalprotein analysisprotein contentprotein expressionproteomicstandem mass spectrometrytransmission electron microscopytumor cellWestern blottingdrug resistanceexosomemembrane microparticleNeoplasmspathologyphysiology
MeSH:Cell-Derived MicroparticlesDrug Resistance, MultipleDrug Resistance, NeoplasmExosomesExtracellular VesiclesHumansNeoplasms

Chemicals and CAS Registry Numbers:

doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0, 433304-61-1

Funding details

Funding sponsor Funding number Acronym
Programa Operacional Temático Factores de Competitividade
Irish Cancer SocietySFRH/BPD/68787/2010,SFRH/BD/98054/2013,SFRH/BD/87646/2012
Fundação para a Ciência e a Tecnologia
See opportunities
Science Foundation Ireland
See opportunities		08/SRC/B1410
Fundação para a Ciência e a Tecnologia
See opportunities		NORTE-07-0162-FEDER-00018,PEst-C/SAU/LA0003/2013,NORTE-07-0162-FEDER-000067

  • 1

    IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. This work is funded by FEDER funds through the Operational Programme for Competitiveness Factors—COMPETE and National Funds through the FCT—Foundation for Science and Technology, under the projects “ PEst-C/SAU/LA0003/2013 ”; NORTE-07-0162-FEDER-00018 — “Contributos para o reforço da capacidade do IPATIMUP enquanto actor do sistema regional de inovação” and NORTE-07-0162-FEDER-000067 — “Reforço e consolidação da capacidade infraestrutural do IPATIMUP para o sistema regional de inovação”, both supported by Programa Operacional Regional do Norte (ON.2 — O Novo Norte), through FEDER funds under the Quadro de Referência Estratégico Nacional (QREN). The proteomic work was also made possible through funding provided in part from awards from Science Foundation Ireland , Grant code 08/SRC/B1410 and the Irish Cancer Society , grant code CCRC13GAL . The authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD grants of VLR and DS ( SFRH/BD/87646/2012 and SFRH/BD/98054/2013 , respectively) and for the post-doc grant of RTL ( SFRH/BPD/68787/2010 ). Appendix A

  • ISSN: 03044165
  • CODEN: BBGSB
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.bbagen.2015.12.011
  • PubMed ID: 26708992
  • Document Type: Article
  • Publisher: Elsevier B.V.

  Vasconcelos, M.H.; IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Rua Julio Amaral de Carvalho, 45, Porto, Portugal;
© Copyright 2019 Elsevier B.V., All rights reserved.

Cited by 21 documents

Álvarez-Arenas, A. , Podolski-Renic, A. , Belmonte-Beitia, J.
Interplay of Darwinian Selection, Lamarckian Induction and Microvesicle Transfer on Drug Resistance in Cancer
(2019) Scientific Reports
Xiang, H.-L. , Chen, Y. , Wang, J.-W.
Enhancing cytotoxicity of daunorubicin on drug-resistant leukaemia cells with microparticle-mediated drug delivery system
(2019) Journal of Microencapsulation
Qu, Y. , Dou, B. , Tan, H.
Tumor microenvironment-driven non-cell-autonomous resistance to antineoplastic treatment
(2019) Molecular Cancer
View details of all 21 citations
Inform me when this document is cited in Scopus:
Set citation alert Set citation feed
{"topic":{"name":"Exosomes; Cells; Recipient cells","id":489,"uri":"Topic/489","prominencePercentile":99.9833,"prominencePercentileString":"99.983","overallScholarlyOutput":0},"dig":"a55542e587f01d1934bc33d5ed74b5a379f3bfb1949a5e862477b90a58cc8506"}

SciVal Topic Prominence

Topic:
Prominence percentile: