Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles

Sousa, Diana; Lima, Raquel T.; Vasconcelos, M. Helena

doi:10.1016/j.molmed.2015.08.002

Cited by 148 publications

(139 citation statements)

References 77 publications

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“…Tumour-derived EVs have been implicated in resistance to other types of therapy in various tumour types [15–19]. By the use of the Cre-based colour switch model, we demonstrated that transfer of active mRNA molecules – such Cre recombinase – among GBM cells occurs in vitro as well as in vivo , and that transferred mRNA can be transcribed into functional molecules once incorporated in recipient cells.…”

Section: Discussionmentioning

confidence: 91%

Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8

Berenguer

Lagerweij

Zhao

et al. 2018

J of Extracellular Vesicle

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Cancer cells release extracellular vesicles (EVs) that contain functional biomolecules such as RNA and proteins. EVs are transferred to recipient cancer cells and can promote tumour progression and therapy resistance. Through RNAi screening, we identified a novel EV uptake mechanism involving a triple interaction between the chemokine receptor CCR8 on the cells, glycans exposed on EVs and the soluble ligand CCL18. This ligand acts as bridging molecule, connecting EVs to cancer cells. We show that glioblastoma EVs promote cell proliferation and resistance to the alkylating agent temozolomide (TMZ). Using in vitro and in vivo stem-like glioblastoma models, we demonstrate that EV-induced phenotypes are neutralised by a small molecule CCR8 inhibitor, R243. Interference with chemokine receptors may offer therapeutic opportunities against EV-mediated cross-talk in glioblastoma.

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Section: Discussionmentioning

confidence: 91%

Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8

Berenguer

Lagerweij

Zhao

et al. 2018

J of Extracellular Vesicle

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“…(Fig. 2) [78]. One of the major roles of these microvesicles is disseminating cancer drug resistance to other non-resistant cancer cells.…”

Section: Expression Of Drug Resistance Proteins and Changes In Drug Mmentioning

confidence: 99%

“…Specifically, these organelles transfer different molecules involved in resistance to other cells by shedding from resistant cells and consequently induce drug resistance to non-resistant cells. Several mediators, such as microRNAs (miRNAs) (miR-100, miR-222, miR-30a, miR-34a, miR-145, miR-485-3p, miR-1228, miR-1246, miR-1308, miR-149, miR-455-3p, miR-638, miR-923, miR-1246, miR-23a, miR-1469, miR-638, miR-1915, miR-2861) and drug efflux pumps (P-gp, ABCG2, MRP1, ABCA3) are transported by these exosomes or microvesicles and when they reached the recipient nonresistant cell, they are fused and internalized by cells via endocytic pathway [78].…”

Section: Expression Of Drug Resistance Proteins and Changes In Drug Mmentioning

confidence: 99%

“…It is suggested that the hydrophobic characteristics of some drugs may enhance their interaction with lipid layer of vesicles and finally result in drug elimination from the cells. Moreover, the presence of several drug transporters in these vesicles, such as ATP7A/B and MRP2, increases the efflux of drugs from cancer cells [78,80]. The presence of drugresistant proteins has been shown in several malignancies, such as P-gp in docetaxel-resistant prostate cancer cells [81] and paclitaxel-resistant ovarian cancer cell line [82], MRP1 transporter in ALL [83], ABCG2 in doxorubicin-resistant breast cancer cells [84], and ABCA3 in rituximab-resistant B-cell lymphoma cells [85], which are responsible for induction of drug resistance in these tumors [78].…”

Section: Extracellular Vesicles and Drug Resistancementioning

confidence: 99%

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Mechanisms of tumor cell resistance to the current targeted-therapy agents

et al. 2016

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Resistance to chemotherapy agents is a major challenge infront of cancer patient treatment and researchers. It is known that several factors, such as multidrug resistance proteins and ATP-binding cassette families, are cell membrane transporters that can efflux several substrates such as chemotherapy agents from the cell cytoplasm. To reduce the adverse effects of chemotherapy agents, various targeted-based cancer therapy (TBCT) agents have been developed. TBCT has revolutionized cancer treatment, and several agents have shown more specific effects on tumor cells than chemotherapies. Small molecule inhibitors and monoclonal antibodies are specific agents that mostly target tumor cells but have low side effects on normal cells. Although these agents have been very useful for cancer treatment, however, the presence of natural and acquired resistance has blunted the advantages of targeted therapies. Therefore, development of new options might be necessary. A better understanding of tumor cell resistance mechanisms to current treatment agents may provide an appropriate platform for developing and improving new treatment modalities. Therefore, in this review, different mechanisms of tumor cell resistance to chemotherapy drugs and current targeted therapies have been described.

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“…Interestingly, cancer tissue-derived exosomes have been shown to contain genomic DNA spanning all chromosomes. This information can be used to determine genomic DNA mutations that will be of diagnostic, prognostic, and theranostic value [189][190][191][192]. In any case, the selective packaging of specific nucleic acids into tailor made vesicles indicates a specialized function.…”

Section: Exosomesmentioning

confidence: 99%

A historical and evolutionary perspective on the biological significance of circulating DNA and extracellular vesicles

Aucamp

Bronkhorst

Badenhorst

et al. 2016

Cell. Mol. Life Sci.

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The discovery of quantitative and qualitative differences of the circulating DNA (cirDNA) between healthy and diseased individuals inclined researchers to investigate these molecules as potential biomarkers for non-invasive diagnosis and prognosis of various pathologies. However, except for some prenatal tests, cirDNA analyses have not been readily translated to clinical practice due to a lack of knowledge regarding its composition, function, and biological and evolutionary origins. We believe that, to fully grasp the nature of cirDNA and the extracellular vesicles (EVs) and protein complexes with which it is associated, it is necessary to probe the early and badly neglected work that contributed to the discovery and development of these concepts. Accordingly, this review consists of a schematic summary of the major events that developed and integrated the concepts of heredity, genetic information, cirDNA, EVs, and protein complexes. Cir-DNA enters target cells and provokes a myriad of gene regulatory effects associated with the messaging functions of various natures, disease progression, somatic genome variation, and transgenerational inheritance. This challenges the traditional views on each of the former topics. All of these discoveries can be traced directly back to the iconic works of Darwin, Lamarck, and their followers. The history of cirDNA that has been revisited here is rich in information that should be considered in clinical practice, when designing new experiments, and should be very useful for generating an empirically up-to-date view of cirDNA and EVs. Furthermore, we hope that it will invite many flights of speculation and stimulate further inquiry into its biological and evolutionary origins.

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Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles

Cited by 148 publications

References 77 publications

Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8

Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8

Mechanisms of tumor cell resistance to the current targeted-therapy agents

A historical and evolutionary perspective on the biological significance of circulating DNA and extracellular vesicles

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