Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers?
Cancer multidrug resistance (MDR) is one of the main mechanisms contributing to therapy failure and mortality. Overexpression of drug transporters of the ABC family (ATP-binding cassette) is a major cause of MDR. Extracellular vesicles (EVs) are nanoparticles released by most cells of the organism i...
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MDPI AG
2023-07-01
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Series: | Life |
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Online Access: | https://www.mdpi.com/2075-1729/13/8/1633 |
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author | María Bucci-Muñoz Aldana Magalí Gola Juan Pablo Rigalli María Paula Ceballos María Laura Ruiz |
author_facet | María Bucci-Muñoz Aldana Magalí Gola Juan Pablo Rigalli María Paula Ceballos María Laura Ruiz |
author_sort | María Bucci-Muñoz |
collection | DOAJ |
description | Cancer multidrug resistance (MDR) is one of the main mechanisms contributing to therapy failure and mortality. Overexpression of drug transporters of the ABC family (ATP-binding cassette) is a major cause of MDR. Extracellular vesicles (EVs) are nanoparticles released by most cells of the organism involved in cell–cell communication. Their cargo mainly comprises, proteins, nucleic acids, and lipids, which are transferred from a donor cell to a target cell and lead to phenotypical changes. In this article, we review the scientific evidence addressing the regulation of ABC transporters by EV-mediated cell–cell communication. MDR transfer from drug-resistant to drug-sensitive cells has been identified in several tumor entities. This was attributed, in some cases, to the direct shuttle of transporter molecules or its coding mRNA between cells. Also, EV-mediated transport of regulatory proteins (e.g., transcription factors) and noncoding RNAs have been indicated to induce MDR. Conversely, the transfer of a drug-sensitive phenotype via EVs has also been reported. Additionally, interactions between non-tumor cells and the tumor cells with an impact on MDR are presented. Finally, we highlight uninvestigated aspects and possible approaches to exploiting this knowledge toward the identification of druggable processes and molecules and, ultimately, the development of novel therapeutic strategies. |
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id | doaj.art-4bc8243e7d0c4be3b57a1ad6cc45a9ee |
institution | Directory Open Access Journal |
issn | 2075-1729 |
language | English |
last_indexed | 2024-03-10T23:47:23Z |
publishDate | 2023-07-01 |
publisher | MDPI AG |
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series | Life |
spelling | doaj.art-4bc8243e7d0c4be3b57a1ad6cc45a9ee2023-11-19T01:53:18ZengMDPI AGLife2075-17292023-07-01138163310.3390/life13081633Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers?María Bucci-Muñoz0Aldana Magalí Gola1Juan Pablo Rigalli2María Paula Ceballos3María Laura Ruiz4Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Instituto de Fisiología Experimental (CONICET), Rosario 2000, ArgentinaFacultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Instituto de Fisiología Experimental (CONICET), Rosario 2000, ArgentinaDepartment of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyFacultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Instituto de Fisiología Experimental (CONICET), Rosario 2000, ArgentinaFacultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Instituto de Fisiología Experimental (CONICET), Rosario 2000, ArgentinaCancer multidrug resistance (MDR) is one of the main mechanisms contributing to therapy failure and mortality. Overexpression of drug transporters of the ABC family (ATP-binding cassette) is a major cause of MDR. Extracellular vesicles (EVs) are nanoparticles released by most cells of the organism involved in cell–cell communication. Their cargo mainly comprises, proteins, nucleic acids, and lipids, which are transferred from a donor cell to a target cell and lead to phenotypical changes. In this article, we review the scientific evidence addressing the regulation of ABC transporters by EV-mediated cell–cell communication. MDR transfer from drug-resistant to drug-sensitive cells has been identified in several tumor entities. This was attributed, in some cases, to the direct shuttle of transporter molecules or its coding mRNA between cells. Also, EV-mediated transport of regulatory proteins (e.g., transcription factors) and noncoding RNAs have been indicated to induce MDR. Conversely, the transfer of a drug-sensitive phenotype via EVs has also been reported. Additionally, interactions between non-tumor cells and the tumor cells with an impact on MDR are presented. Finally, we highlight uninvestigated aspects and possible approaches to exploiting this knowledge toward the identification of druggable processes and molecules and, ultimately, the development of novel therapeutic strategies.https://www.mdpi.com/2075-1729/13/8/1633ABC transportersdrug resistanceextracellular vesiclesP-glycoproteinbreast cancer resistance proteinmultidrug resistance-associated protein |
spellingShingle | María Bucci-Muñoz Aldana Magalí Gola Juan Pablo Rigalli María Paula Ceballos María Laura Ruiz Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers? Life ABC transporters drug resistance extracellular vesicles P-glycoprotein breast cancer resistance protein multidrug resistance-associated protein |
title | Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers? |
title_full | Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers? |
title_fullStr | Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers? |
title_full_unstemmed | Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers? |
title_short | Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers? |
title_sort | extracellular vesicles and cancer multidrug resistance undesirable intercellular messengers |
topic | ABC transporters drug resistance extracellular vesicles P-glycoprotein breast cancer resistance protein multidrug resistance-associated protein |
url | https://www.mdpi.com/2075-1729/13/8/1633 |
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