Page 69 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

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Studying the ability of tumor multidrug-resistant cells and drug-sensitive counterparts to
release and capture extracellular vesicles

1,2
Diana Sousa 1,2,3 , Raquel T. Lima 1,2,4,5 , Cristina P. R. Xavier , Vanessa Lopes-Rodrigues 1,2,6 , Esperanza
7,8
7
7
Gonzalez , Félix Royo , Juan M. Falcón-Pérez , M. Helena Vasconcelos 1,2,3 *
1 i3S- Instituto de Investigação e Inovação em Saúde, Portugal
2
Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of
Porto, Portugal
3
Department of Biological Sciences, FFUP - Faculty of Pharmacy of the University of Porto, Portugal
4
Department of Pathology, FMUP - Faculty of Medicine of the University of Porto, Portugal
5
Cancer Signaling & Metabolism Group, IPATIMUP- Institute of Molecular Pathology and Immunology of the
University of Porto, Portugal
6
ICBAS-UP – Institute of Biomedical Sciences Abel Salazar of the University of Porto, Portugal
7
Exosomes Lab. & Metabolomics Platform, CIC bioGUNE, CIBERehd, Spain
8
IKERBASQUE Basque Foundation for Science, Spain

Background: Multidrug resistance (MDR) is one of the main challenges for cancer treatment efficacy. MDR
is a phenomenon by which tumor cells develop cross-resistance to several unrelated drugs and is frequently
caused by an overexpression of drug-efflux pumps, particularly P-glycoprotein (P-gp). Interestingly, in
different tumor models, Extracellular Vesicles (EVs) carrying P-gp in their cargo were found to promote the
horizontal transfer or MDR phenotype between MDR cells and drug-sensitive cells. The aim of the present
work was to unravel the mechanisms involved in the release of EVs by MDR cells and their uptake by drug-
sensitive counterparts. Material and methods: To achieve this, two pairs of cell lines from two different
tumor models [chronic myeloid leukemia (CML) and non-small cell lung cancer (NSCLC)] were used,
consisting of a drug-sensitive cell line and its MDR (P-gp overexpressing) counterpart. EVs released by those
pairs of cell lines were isolated by ultracentrifugation and properly characterized by some of us. Results:
Our results showed that MDR cells released more EVs than their drug-sensitive counterparts and also that
drug-sensitive cells captured more EVs than their MDR counterparts. This difference (in the release and
capture of EVs by drug-sensitive and MDR cells) may be associated with differences in the endocytic
pathway. Importantly, manipulation of the recycling pathway influenced the response of drug-sensitive
cells to doxorubicin treatment. Conclusion: Increasing knowledge about the players involved may
contribute to identifying targets to overcome the horizontal transfer of MDR.
Acknowledgements: This work is a result of the project NORTE-01-0145-FEDER-000029, supported by NORTE 2020,
under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). The
M.H.V. group is supported by FEDER – Fundo Europeu de Desenvolvimento Regional through COMPETE 2020 and by
FCT - Foundation for Science and Technology, in the framework of project POCI-01-0145-FEDER-030457. The authors
thank Spanish MINECO (SAF2015-66312 to JMF), REDIEX (Spanish Excellence Network in Exosomes) and Severo Ochoa
Excellence Accreditation (SEV-2016-0644). Also, the Portuguese Foundation for Science and Technology for the PhD
grant of DS (SFRH/BD/98054/2013) and the post-doc grant of CPRX (SFRH/BPD/122871/2016), the European COST
Action (ME-HaD, BM1202) for a short-term mission fellowship and GEIVEX for a mobility fellowship which allowed the
work of DS in CICbioGUNE.

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