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

Lopes-Rodrigues, Vanessa; Luca, Alessio Di; Sousa, Diana; Seca, Hugo; Meleady, Paula; Henry, Michael; Lima, Raquel T.; O’Connor, Robert; Vasconcelos, M. Helena

doi:10.1016/j.bbagen.2015.12.011

Cited by 46 publications

(45 citation statements)

References 49 publications

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“…Fusion of EVs with target cells was originally thought to serve primarily to initiate immune response, however, it is now known that EVs derived from tumor cells can serve nefarious purposes, such as transfer of drug resistance mechanisms and promotion of metastasis [46] and vascular development, a key hallmark of tumor growth [47]. …”

Section: Liquid Biopsy: Technologies Advancing Personalized Medicinementioning

confidence: 99%

“…In addition, loss of material during washes and the type of rotor used for sample processing can confound the ability to obtain pure samples [47]. Other methods exist, such as flow cytometry, field-flow fractionation, spectroscopy, and nanoparticle tracking [48,49], yet no ideal method has emerged, mainly due to the heterogeneity of EVs and difficulties in distinguishing between fractions based on size, structure, and protein composition [46]. …”

Section: Liquid Biopsy: Technologies Advancing Personalized Medicinementioning

confidence: 99%

“…It has been observed that tumor-derived EVs originating from drug-sensitive cells are smaller and more exosomal in morphology and protein expression than those produced by drug-resistant cells, which contain smaller amounts of exosome-associated proteins. In addition, multi-drug resistant cells have been reported to produce more EVs than drug-sensitive cells [46]. The contents of the vesicles may also point to the cells of origin, which can be useful in assessing tumor heterogeneity, as highlighted in a study by Skog, et al In the study, the glioblastoma-associated type III EGFR variant (EGFRvIII), which lacks a portion of the EGFR extracellular ligand binding domain, was detected in sera EVs of glioblastoma patients whose biopsies were EGFRvIII-negative.…”

Section: Liquid Biopsy: Technologies Advancing Personalized Medicinementioning

confidence: 99%

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Technological advances in precision medicine and drug development

Maggi

Patterson

Montagna

2016

Expert Review of Precision Medicine and Drug Development

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New technologies are rapidly becoming available to expand the arsenal of tools accessible for precision medicine and to support the development of new therapeutics. Advances in liquid biopsies, which analyze cells, DNA, RNA, proteins, or vesicles isolated from the blood, have gained particular interest for their uses in acquiring information reflecting the biology of tumors and metastatic tissues. Through advancements in DNA sequencing that have merged unprecedented accuracy with affordable cost, personalized treatments based on genetic variations are becoming a real possibility. Extraordinary progress has been achieved in the development of biological therapies aimed to even further advance personalized treatments. We provide a summary of current and future applications of blood based liquid biopsies and how new technologies are utilized for the development of biological therapeutic treatments. We discuss current and future sequencing methods with an emphasis on how technological advances will support the progress in the field of precision medicine.

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Section: Liquid Biopsy: Technologies Advancing Personalized Medicinementioning

confidence: 99%

Section: Liquid Biopsy: Technologies Advancing Personalized Medicinementioning

confidence: 99%

Section: Liquid Biopsy: Technologies Advancing Personalized Medicinementioning

confidence: 99%

See 1 more Smart Citation

Technological advances in precision medicine and drug development

Maggi

Patterson

Montagna

2016

Expert Review of Precision Medicine and Drug Development

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“…EVs can also contribute to drug resistance via various mechanisms, including the sequestration of drugs (34,35) and the transfer of proteins or RNA (36)(37)(38)(39) (40)(41)(42)(43)(44)(45). The morphology and the proteomic profile of EVs from multi-drug resistant tumours has been shown to be different from those from sensitive tumours (46) and EVs could be used as prognostic and diagnostic biomarkers in cancer (47).…”

mentioning

confidence: 99%

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Samuel

Mulcahy

Furlong

et al. 2017

Phil. Trans. R. Soc. B

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Ovarian cancer has a poor overall survival that is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naive cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested. Here we show that treatment of cells with cisplatin led to the release of EVs that could induce invasion and increased resistance when taken up by bystander cells. This coincided with changes in p38 and JNK signalling, suggesting that these pathways may be involved in mediating the effects. We also show that EV uptake inhibitors could prevent this EV-mediated adaptive response and thus sensitize cells in vitro to the effects of cisplatin. Our results suggest that preventing pro-tumourigenic EV cross-talk during chemotherapy is a potential therapeutic target for improving outcome in ovarian cancer patients. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

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“…These mechanisms include the lowering of the intracellular drug concentration, activation of detoxification enzymes, changes in drug metabolism inside of the cell and the inhibition of cancer cell apoptosis (33,34). The most well-known and frequently described MDR mechanism is the increased expression of transport proteins at the membrane of cancer cells (35). Therefore, studies on substances that enable cancer cell sensitisation to cytostatics are necessary.…”

Section: Discussionmentioning

confidence: 99%

Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol

et al. 2018

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Abstract. Multidrug resistance (MDR) is a notable problem in the use of chemotherapy. Therefore, studies aimed at identifying substances capable of overcoming resistance of cancer cells are required. Examples of these compounds are polyphenols, including resveratrol, that exert a range of various biological activities. The aim of the present study was to demonstrate the effect of 3,5,4'-trihydroxy-trans-stilbene (resveratrol) on the expression of ATP binding cassette subfamily B member 1, Annexin A1 (ANXA1) and thioredoxin (TXN) genes, and the proteins encoded by these genes, which are associated with MDR. The experiments were performed in human gastric cancer cell lines EPG85-257RDB (RDB) and EPG85-257RNOV (RNOV), which are resistant to daunorubicin and mitoxantrone, respectively, in addition to EPG85-257P (control), which is sensitive to cytostatic drugs. Cells were treated with 30 or 50 µM resveratrol for 72 h and changes in the expression levels of the genes were analysed with the use of a reverse transcription-quantitative polymerase chain reaction. The cellular levels of P-glycoprotein (P-gp), ANXA1 and TXN were evaluated using immunofluorescence and western blot analysis. Resveratrol in both concentrations has been shown to have a statistically significant influence on expression of the mentioned genes, compared with untreated cells. In RDB cells, resveratrol reduced the expression level of all analyzed genes, compared with untreated cells. Similar results at the protein level were obtained for P-gp and TXN. In turn, in the RNOV cell line, resveratrol reduced TXN expression at mRNA and protein levels, compared with untreated cells. The results of the present study indicate that resveratrol may reduce the resistance of cancer cells by affecting the expression of a number of the genes and proteins associated with MDR. IntroductionResveratrol belongs to the stilbenoid group of polyphenols, possessing two phenol rings linked to each other by an ethylene bridge (1). In 1940, resveratrol was isolated from the root of Veratrum grandiflorum (1,2). A primary dietary source of resveratrol is red wine, as a very high resveratrol concentration is present in the skin of red grapes (50-100 µg/g) (3). In natural conditions, resveratrol is synthesized by plants in response to external environmental factors, including ultraviolet radiation and heavy metals (3,4). Resveratrol is identified in two isomeric forms, cis and trans-resveratrol ( Fig. 1) (5,6).The trans form is dominant in terms of its prevalence and biological activity (7). The hydrophobic nature of resveratrol considerably contributes to its limited bioavailability (8).Owing to the varied biological activity of resveratrol, it has been the subject of numerous studies aimed at revealing its health-enhancing properties, and its use in prevention and treatment of many diseases (1,3,5,9). The results of in vitro and in vivo studies have proved that resveratrol exhibits anticancer activity at all three stages of the oncogenic process: initiation, promotion and progr...

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

Cited by 46 publications

References 49 publications

Technological advances in precision medicine and drug development

Technological advances in precision medicine and drug development

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol

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