{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:26:24Z","timestamp":1761294384193,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"N2020 and PORTUGAL2020","award":["NORTE-01-0145-FEDER-000029"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000029"]}]},{"name":"Spanish MINECO","award":["SAF2015-66312"],"award-info":[{"award-number":["SAF2015-66312"]}]},{"name":"Severo Ochoa Excellence Accreditation","award":["SEV-2016-0644"],"award-info":[{"award-number":["SEV-2016-0644"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["SFRH\/BD\/98054\/2013"],"award-info":[{"award-number":["SFRH\/BD\/98054\/2013"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT) and Fundo Social Europeu (FSE)","award":["SFRH\/BPD\/122871\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/122871\/2016"]}]},{"name":"European COST Action","award":["ECOST-STSM-BM1202-150317-083396"],"award-info":[{"award-number":["ECOST-STSM-BM1202-150317-083396"]}]},{"name":"GEIVEX","award":["mobility fellowship"],"award-info":[{"award-number":["mobility fellowship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cancer multidrug resistance (MDR) is one of the main challenges for cancer treatment efficacy. MDR is a phenomenon by which tumor cells become resistant to several unrelated drugs. Some studies have previously described the important role of extracellular vesicles (EVs) in the dissemination of a MDR phenotype. EVs\u2019 cargo may include different players of MDR, such as microRNAS and drug-efflux pumps, which may be transferred from donor MDR cells to recipient drug-sensitive counterparts. The present work aimed to: (i) compare the ability of drug-sensitive and their MDR counterpart cells to release and capture EVs and (ii) study and relate those differences with possible distinct fate of the endocytic pathway in these counterpart cells. Our results showed that MDR cells released more EVs than their drug-sensitive counterparts and also that the drug-sensitive cells captured more EVs than their MDR counterparts. This difference in the release and capture of EVs may be associated with differences in the endocytic pathway between drug-sensitive and MDR cells. Importantly, manipulation of the recycling pathway influenced the response of drug-sensitive cells to doxorubicin treatment.<\/jats:p>","DOI":"10.3390\/cells10112886","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:49:52Z","timestamp":1635292192000},"page":"2886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Different Ability of Multidrug-Resistant and -Sensitive Counterpart Cells to Release and Capture Extracellular Vesicles"],"prefix":"10.3390","volume":"10","author":[{"given":"Diana","family":"Sousa","sequence":"first","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Biological Sciences, FFUP\u2014Faculty of Pharmacy of the University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-9659","authenticated-orcid":false,"given":"Raquel T.","family":"Lima","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Pathology, FMUP\u2014Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Cancer Signaling & Metabolism Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Vanessa","family":"Lopes-Rodrigues","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS-UP\u2014Institute of Biomedical Sciences Abel Salazar of the University of Porto, 4099-003 Porto, Portugal"}]},{"given":"Esperanza","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Exosomes Lab. & Metabolomics Platform, CIC bioGUNE, CIBERehd, 28160 Derio, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-4165","authenticated-orcid":false,"given":"F\u00e9lix","family":"Royo","sequence":"additional","affiliation":[{"name":"Exosomes Lab. & Metabolomics Platform, CIC bioGUNE, CIBERehd, 28160 Derio, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-1917","authenticated-orcid":false,"given":"Cristina P. R.","family":"Xavier","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-0670","authenticated-orcid":false,"given":"Juan M.","family":"Falc\u00f3n-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Exosomes Lab. & Metabolomics Platform, CIC bioGUNE, CIBERehd, 28160 Derio, Spain"},{"name":"IKERBASQUE Basque Foundation for Science, 48013 Bilbao, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-4643","authenticated-orcid":false,"given":"M. Helena","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Biological Sciences, FFUP\u2014Faculty of Pharmacy of the University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.2174\/1568009616666151113120705","article-title":"Understanding Cancer Drug Resistance by Developing and Studying Resistant Cell Line Models","volume":"16","author":"Xavier","year":"2016","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-1-60761-416-6_4","article-title":"Mechanisms of multidrug resistance in cancer","volume":"596","author":"Gillet","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100645","DOI":"10.1016\/j.drup.2019.100645","article-title":"The multi-factorial nature of clinical multidrug resistance in cancer","volume":"46","author":"Assaraf","year":"2019","journal-title":"Drug Resist. Updat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1073\/pnas.0401851102","article-title":"Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells","volume":"102","author":"Levchenko","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1038\/leu.2009.76","article-title":"Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells","volume":"23","author":"Bebawy","year":"2009","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1002\/pros.22848","article-title":"miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression","volume":"74","author":"Corcoran","year":"2014","journal-title":"Prostate"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1158\/1541-7786.MCR-13-0636","article-title":"Involvement of Extracellular Vesicle Long Noncoding RNA (linc-VLDLR) in Tumor Cell Responses to Chemotherapy","volume":"12","author":"Takahashi","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.phrs.2013.07.009","article-title":"Microparticles mediate MRP1 intercellular transfer and the re-templating of intrinsic resistance pathways","volume":"76","author":"Lu","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10773","DOI":"10.1007\/s13277-014-2377-z","article-title":"Exosomes mediate drug resistance transfer in MCF-7 breast cancer cells and a probable mechanism is delivery of P-glycoprotein","volume":"35","author":"Lv","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejphar.2014.05.026","article-title":"Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780 human ovarian cancer cells, conferring paclitaxel-resistance","volume":"738","author":"Zhang","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fontana, F., Carollo, E., Melling, G., and Carter, D. (2021). Extracellular Vesicles: Emerging Modulators of Cancer Drug Resistance. Cancers, 13.","DOI":"10.3390\/cancers13040749"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e257","DOI":"10.1002\/ctm2.257","article-title":"The roles of exosomes in cancer drug resistance and its therapeutic application","volume":"10","author":"Li","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2019.07.003","article-title":"Exosomes and their role in tumorigenesis and anticancer drug resistance","volume":"45","author":"Milman","year":"2019","journal-title":"Drug Resist. Updat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20160479","DOI":"10.1098\/rstb.2016.0479","article-title":"Why the need and how to approach the functional diversity of extracellular vesicles","volume":"373","author":"Tkach","year":"2018","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1038\/ncomms4477","article-title":"Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2","volume":"5","author":"Ghossoub","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"jcs216499","DOI":"10.1242\/jcs.216499","article-title":"The enigmatic endosome\u2014Sorting the ins and outs of endocytic trafficking","volume":"131","author":"Naslavsky","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a016857","DOI":"10.1101\/cshperspect.a016857","article-title":"The Complex Ultrastructure of the Endolysosomal System","volume":"6","author":"Klumperman","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.03.034","article-title":"Endosome maturation, transport and functions","volume":"31","author":"Scott","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sousa, D., Matthiesen, R., Lima, R.T., and Vasconcelos, M.H. (2020). Deep Sequencing Analysis Reveals Distinctive Non-Coding RNAs When Comparing Tumor Multidrug-Resistant Cells and Extracellular Vesicles with Drug-Sensitive Counterparts. Cancers, 12.","DOI":"10.3390\/cancers12010200"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.bbagen.2015.12.011","article-title":"Multidrug resistant tumour cells shed more microvesicle-like EVs and less exosomes than their drug-sensitive counterpart cells","volume":"1860","author":"Sousa","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.3892\/or.2012.1967","article-title":"Exosomes secreted from human colorectal cancer cell lines contain mRNAs, microRNAs and natural antisense RNAs, that can transfer into the human hepatoma HepG2 and lung cancer A549 cell lines","volume":"28","author":"Chiba","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12918","DOI":"10.1016\/S0021-9258(18)99963-1","article-title":"The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems","volume":"269","author":"Plank","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5243","DOI":"10.1242\/jcs.02633","article-title":"Distribution and dynamics of Lamp1-containing endocytic organelles in fibroblasts deficient in BLOC-3","volume":"118","author":"Nazarian","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41580-018-0053-7","article-title":"To degrade or not to degrade: Mechanisms and significance of endocytic recycling","volume":"19","author":"Cullen","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.bbrc.2009.08.067","article-title":"Cytoplasmic phospholipase A2 antagonists inhibit multiple endocytic membrane trafficking pathways","volume":"388","author":"Doody","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.molmed.2015.08.002","article-title":"Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles","volume":"21","author":"Sousa","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xiao, X., Yu, S., Li, S., Wu, J., Ma, R., Cao, H., Zhu, Y., and Feng, J. (2014). Exosomes: Decreased sensitivity of lung cancer A549 cells to cisplatin. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089534"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2407-12-421","article-title":"Hypoxic enhancement of exosome release by breast cancer cells","volume":"12","author":"King","year":"2012","journal-title":"BMC Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bbrc.2016.10.019","article-title":"Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress","volume":"480","author":"Kanemoto","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.dib.2016.02.004","article-title":"Data supporting the shedding of larger extracellular vesicles by multidrug resistant tumour cells","volume":"6","author":"Sousa","year":"2016","journal-title":"Data Brief"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2174\/1568009615666150225121508","article-title":"Targeting Microparticle Biogenesis: A Novel Approach to the Circumvention of Cancer Multidrug Resistance","volume":"15","author":"Roseblade","year":"2015","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/j.bcp.2012.01.033","article-title":"Inhibition of the PI3K-Akt signaling pathway disrupts ABCG2-rich extracellular vesicles and overcomes multidrug resistance in breast cancer cells","volume":"83","author":"Sladkevich","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1582-4934.2011.01316.x","article-title":"Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients","volume":"16","author":"Yin","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15336","DOI":"10.1073\/pnas.1102855108","article-title":"Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3","volume":"108","author":"Aung","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1083\/jcb.201810134","article-title":"Comprehensive knockout analysis of the Rab family GTPases in epithelial cells","volume":"218","author":"Homma","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1242\/jcs.115.12.2505","article-title":"The exosome pathway in K562 cells is regulated by Rab11","volume":"115","author":"Savina","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24764","DOI":"10.1074\/jbc.M113.474023","article-title":"Lipid Segregation and Membrane Budding Induced by the Peripheral Membrane Binding Protein Annexin A2*","volume":"288","author":"Pejic","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/19336918.2016.1236899","article-title":"Mechanisms and functions of extracellular vesicle release in vivo\u2014What we can learn from flies and worms","volume":"11","author":"Beer","year":"2017","journal-title":"Cell Adhes. Migr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1091\/mbc.e06-12-1147","article-title":"The Clathrin Adaptor Complex AP-1 Binds HIV-1 and MLV Gag and Facilitates Their Budding","volume":"18","author":"Camus","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1111\/j.1600-0854.2008.00796.x","article-title":"Human Herpesvirus-6 Induces MVB Formation, and Virus Egress Occurs by an Exosomal Release Pathway","volume":"9","author":"Mori","year":"2008","journal-title":"Traffic"},{"key":"ref_43","first-page":"G863","article-title":"Rab11, but not Rab4, facilitates cyclic AMP- and tauroursodeoxycholate-induced MRP2 translocation to the plasma membrane","volume":"307","author":"Park","year":"2014","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1097\/MPA.0000000000000910","article-title":"Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells","volume":"46","author":"Li","year":"2017","journal-title":"Pancreas"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1080\/00498254.2020.1716107","article-title":"Modulation of ABCG2 surface expression by Rab5 and Rab21 to overcome multidrug resistance in cancer cells","volume":"50","author":"Yousaf","year":"2020","journal-title":"Xenobiotica"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms8029","article-title":"Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters","volume":"6","author":"Lai","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/j.biocel.2012.06.018","article-title":"Toward tailored exosomes: The exosomal tetraspanin web contributes to target cell selection","volume":"44","author":"Rana","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1478-811X-10-37","article-title":"Tumor-exosomes and leukocyte activation: An ambivalent crosstalk","volume":"10","author":"Zech","year":"2012","journal-title":"Cell Commun. Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"24641","DOI":"10.3402\/jev.v3.24641","article-title":"Routes and mechanisms of extracellular vesicle uptake","volume":"3","author":"Mulcahy","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10571-016-0366-z","article-title":"Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake","volume":"36","author":"Abels","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3390\/membranes4030356","article-title":"Endocytic Trafficking of Membrane-Bound Cargo: A Flotillin Point of View","volume":"4","author":"Meister","year":"2014","journal-title":"Membranes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1242\/jcs.092015","article-title":"The roles of flotillin microdomains\u2014Endocytosis and beyond","volume":"124","author":"Otto","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"srep44541","DOI":"10.1038\/srep44541","article-title":"Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles","volume":"7","author":"Mleczko","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0169-409X(01)00144-2","article-title":"Upregulation of caveolin in multidrug resistant cancer cells: Functional implications","volume":"49","author":"Lavie","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1038\/emboj.2011.286","article-title":"Endosome maturation","volume":"30","author":"Huotari","year":"2011","journal-title":"EMBO J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1158\/0008-5472.CAN-05-3436","article-title":"Endocytic Recycling Compartments Altered in Cisplatin-Resistant Cancer Cells","volume":"66","author":"Liang","year":"2006","journal-title":"Cancer Res."},{"key":"ref_57","first-page":"5909","article-title":"Mislocalization of membrane proteins associated with multidrug resistance in cisplatin-resistant cancer cell lines","volume":"63","author":"Liang","year":"2003","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/sj.bjc.6600861","article-title":"Reduced endocytosis and altered lysosome function in cisplatin-resistant cell lines","volume":"88","author":"Chauhan","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3389\/fonc.2014.00306","article-title":"Reduced Intracellular Drug Accumulation in Drug-Resistant Leukemia Cells is Not Only Solely Due to MDR-Mediated Efflux but also to Decreased Uptake","volume":"4","author":"Pisco","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Guerra, F., Paiano, A., Migoni, D., Girolimetti, G., Perrone, A.M., De Iaco, P., Fanizzi, F.P., Gasparre, G., and Bucci, C. (2019). Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment and Extracellular Vesicular Secretion. Cancers, 11.","DOI":"10.3390\/cancers11010052"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-019-1114-z","article-title":"Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance","volume":"18","author":"Wang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.7150\/thno.47996","article-title":"Endocytic pathway inhibition attenuates extracellular vesicle-induced reduction of chemosensitivity to bortezomib in multiple myeloma cells","volume":"11","author":"Tu","year":"2021","journal-title":"Theranostics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1179\/joc.2006.18.1.66","article-title":"Induced Resistance in the Human Non-Small Cell Lung Carcinoma (NCI-H460) Cell Line In Vitro by Anticancer Drugs","volume":"18","author":"Pesic","year":"2006","journal-title":"J. Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s00280-013-2247-1","article-title":"Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing","volume":"72","author":"Jadranin","year":"2013","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_65","first-page":"825","article-title":"Daunorubicin uptake by leukemic cells: Correlations with treatment outcome and mdr1 expression","volume":"7","author":"Marie","year":"1993","journal-title":"Leukemia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1179\/102453311X12940641877803","article-title":"Simultaneous targeting of P-gp and XIAP with siRNAs increases sensitivity of P-gp overexpressing CML cells to imatinib","volume":"16","author":"Seca","year":"2011","journal-title":"Hematology"},{"key":"ref_67","first-page":"3","article-title":"Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids","volume":"30","author":"Amigorena","year":"2006","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.indcrop.2014.05.009","article-title":"Flower extracts of Filipendula ulmaria (L.) Maxim inhibit the proliferation of the NCI-H460 tumour cell line","volume":"59","author":"Lima","year":"2014","journal-title":"Indust. Crops Prod."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Sommer, C., Str\u00e4hle, C., K\u00f6the, U., and Hamprecht, F.A. (April, January 30). ilastik: Interactive Learning and Segmentation Toolkit. Proceedings of the 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, Chicago, IL, USA.","DOI":"10.1109\/ISBI.2011.5872394"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"McQuin, C., Goodman, A., Chernyshev, V., Kamentsky, L., Cimini, B.A., Karhohs, K.W., Doan, M., Ding, L., Rafelski, S.M., and Thirstrup, D. (2018). CellProfiler 3.0: Next-generation image processing for biology. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2005970"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Barbosa, J., Lima, R.T., Sousa, D., Gomes, A.S., Palmeira, A., Seca, H., Choosang, K., Pakkong, P., Bousbaa, H., and Pinto, M.M.M. (2016). Screening a Small Library of Xanthones for Antitumor Activity and Identification of a Hit Compound which Induces Apoptosis. Molecules, 21.","DOI":"10.3390\/molecules21010081"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/2886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:23:59Z","timestamp":1760167439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/2886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":71,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cells10112886"],"URL":"https:\/\/doi.org\/10.3390\/cells10112886","relation":{},"ISSN":["2073-4409"],"issn-type":[{"type":"electronic","value":"2073-4409"}],"subject":[],"published":{"date-parts":[[2021,10,26]]}}}