Journal of extracellular biology最新文献

{"title":"Cardiomyocyte intercellular signalling increases oxidative stress and reprograms the global- and phospho-proteome of cardiac fibroblasts","authors":"Bethany Claridge,&nbsp;Alin Rai,&nbsp;Jarmon G. Lees,&nbsp;Haoyun Fang,&nbsp;Shiang Y. Lim,&nbsp;David W. Greening","doi":"10.1002/jex2.125","DOIUrl":"https://doi.org/10.1002/jex2.125","url":null,"abstract":"<p>Pathological reprogramming of cardiomyocyte and fibroblast proteome landscapes drive the initiation and progression of cardiac fibrosis. Although the secretome of dysfunctional cardiomyocytes is emerging as an important driver of pathological fibroblast reprogramming, our understanding of the downstream molecular players remains limited. Here, we show that cardiac fibroblast activation (αSMA⁺) and oxidative stress mediated by the secretome of TGFβ-stimulated cardiomyocytes is associated with a profound reprogramming of their proteome and phosphoproteome landscape. Within the fibroblast global proteome there was a striking dysregulation of proteins implicated in extracellular matrix, protein localisation/metabolism, KEAP1-NFE2L2 pathway, lysosomes, carbohydrate metabolism, and transcriptional regulation. Kinase substrate enrichment analysis of phosphopeptides revealed potential role of kinases (CK2, CDK2, PKC, GSK3B) during this remodelling. We verified upregulated activity of casein kinase 2 (CK2) in secretome-treated fibroblasts, and pharmacological CK2 inhibitor TBB (4,5,6,7-Tetrabromobenzotriazole) significantly abrogated fibroblast activation and oxidative stress. Our data provides molecular insights into cardiomyocyte to cardiac fibroblast crosstalk, and the potential role of CK2 in regulating cardiac fibroblast activation and oxidative stress.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138468709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer cell invasion alters the protein profile of extracellular vesicles","authors":"Jens C. Luoto,&nbsp;Leila S. Coelho-Rato,&nbsp;Cecilia Jungarå,&nbsp;Sara H. Bengs,&nbsp;Jannica Roininen,&nbsp;John E. Eriksson,&nbsp;Lea Sistonen,&nbsp;Eva Henriksson","doi":"10.1002/jex2.124","DOIUrl":"https://doi.org/10.1002/jex2.124","url":null,"abstract":"<p>Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long-range signalling of cancer metastasis. The onset of invasion is the key step of the metastatic cascade, but the secretion of EVs has remained unexplored at that stage due to technical challenges. In this study, we present a platform to track EVs over the course of invasive development of human prostate cancer cell (PC3) tumoroids utilizing in vivo-mimicking extracellular matrix-based 3D cultures. Using this EV production method, combined with proteomic profiling, we show that PC3 tumoroids secrete EVs with previously undefined protein cargo. Intriguingly, an increase in EV amounts and extensive changes in the EV protein composition were detected upon invasive transition of the tumoroids. The changes in EV protein cargo were counteracted by chemical inhibition of invasion. These results reveal the impact of the tumoroids’ invasive status on EV secretion and cargo, and highlight the necessity of in vivo-mimicking conditions for uncovering novel cancer-derived EV components.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138439847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles from bodily fluids for the accurate diagnosis of Parkinson's disease and related disorders: A systematic review and diagnostic meta-analysis","authors":"Hash Brown Taha,&nbsp;Aleksander Bogoniewski","doi":"10.1002/jex2.121","DOIUrl":"https://doi.org/10.1002/jex2.121","url":null,"abstract":"<p>Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are often misdiagnosed due to overlapping symptoms and the absence of precise biomarkers. Furthermore, there are no current methods to ascertain the progression and conversion of prodromal conditions such as REM behaviour disorder (RBD). Extracellular vesicles (EVs), containing a mixture of biomolecules, have emerged as potential sources for parkinsonian diagnostics. However, inconsistencies in previous studies have left their diagnostic potential unclear. We conducted a meta-analysis, following PRISMA guidelines, to assess the diagnostic accuracy of general EVs isolated from various bodily fluids, including cerebrospinal fluid (CSF), plasma, serum, urine or saliva, in differentiating patients with parkinsonian disorders from healthy controls (HCs). The meta-analysis included 21 studies encompassing 1285 patients with PD, 24 with MSA, 105 with DLB, 99 with PSP, 101 with RBD and 783 HCs. Further analyses were conducted only for patients with PD versus HCs, given the limited number for other comparisons. Using bivariate and hierarchal receiver operating characteristics (HSROC) models, the meta-analysis revealed moderate diagnostic accuracy in distinguishing patients with PD from HCs, with substantial heterogeneity and publication bias. The trim-and-fill method revealed at least two missing studies with null or low diagnostic accuracy. CSF-EVs showed better overall diagnostic accuracy, while plasma-EVs had the lowest performance. General EVs demonstrated higher diagnostic accuracy compared to CNS-originating EVs, which are more time-consuming, labour- and cost-intensive to isolate. In conclusion, while holding promise, utilizing biomarkers in general EVs for PD diagnosis remains unfeasible due to existing challenges. The focus should shift toward harmonizing the field through standardization, collaboration, and rigorous validation. Current efforts by the International Society For Extracellular Vesicles (ISEV) aim to enhance the accuracy and reproducibility of EV-related research through rigor and standardization, aiming to bridge the gap between theory and practical clinical application.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"109168392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate-derived circulating microRNAs add prognostic value to prostate cancer risk calculators","authors":"Morgan L. Zenner,&nbsp;Brenna Kirkpatrick,&nbsp;Trevor R. Leonardo,&nbsp;Michael J. Schlicht,&nbsp;Alejandra Cavazos Saldana,&nbsp;Candice Loitz,&nbsp;Klara Valyi-Nagy,&nbsp;Mark Maienschein-Cline,&nbsp;Peter H. Gann,&nbsp;Michael Abern,&nbsp;Larisa Nonn","doi":"10.1002/jex2.122","DOIUrl":"10.1002/jex2.122","url":null,"abstract":"<p>Prostate cancer is the second leading cause of malignancy-related deaths among American men. Active surveillance is a safe option for many men with less aggressive disease, yet definitively determining low-risk cancer is challenging with biopsy alone. Herein, we sought to identify prostate-derived microRNAs in patient sera and serum extracellular vesicles, and determine if those microRNAs improve upon the current clinical risk calculators for prostate cancer prognosis before and after biopsy. Prostate-derived intracellular and extracellular vesicle-contained microRNAs were identified by small RNA sequencing of prostate cancer patient explants and primary cells. Abundant microRNAs were included in a custom microRNA PCR panel that was queried in whole serum and serum extracellular vesicles from a diverse cohort of men diagnosed with prostate cancer. The levels of these circulating microRNAs significantly differed between indolent and aggressive disease and improved the area under the curve for pretreatment nomograms of prostate cancer disease risk. The microRNAs within the extracellular vesicles were the most informative and improved the AUC to 0.739 compared to the existing nomogram alone, which has an AUC of 0.561. The microRNAs in the whole serum improved it to AUC 0.675. In summary, quantifying microRNAs circulating in extracellular vesicles is a clinically feasible assay that may provide additional information for assessing prostate cancer risk stratification.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human red blood cells release microvesicles with distinct sizes and protein composition that alter neutrophil phagocytosis","authors":"Getulio Pereira de Oliveira Junior,&nbsp;Joshua A. Welsh,&nbsp;Brandy Pinckney,&nbsp;Cintia C. Palu,&nbsp;Shulin Lu,&nbsp;Alan Zimmerman,&nbsp;Raquel Hora Barbosa,&nbsp;Parul Sahu,&nbsp;Maeesha Noshin,&nbsp;Suryaram Gummuluru,&nbsp;John Tigges,&nbsp;Jennifer Clare Jones,&nbsp;Alexander R. Ivanov,&nbsp;Ionita C. Ghiran","doi":"10.1002/jex2.107","DOIUrl":"https://doi.org/10.1002/jex2.107","url":null,"abstract":"<p>Extracellular vesicles (EVs) are membrane-bound structures released by cells and tissues into biofluids, involved in cell-cell communication. In humans, circulating red blood cells (RBCs), represent the most common cell-type in the body, generating daily large numbers of microvesicles. In vitro, RBC vesiculation can be mimicked by stimulating RBCs with calcium ionophores, such as ionomycin and A23187. The fate of microvesicles released during in vivo aging of RBCs and their interactions with circulating cells is hitherto unknown. Using SEC plus DEG isolation methods, we have found that human RBCs generate microvesicles with two distinct sizes, densities and protein composition, identified by flow cytometry, and MRPS, and further validated by immune TEM. Furthermore, proteomic analysis revealed that RBC-derived microvesicles (RBC-MVs) are enriched in proteins with important functions in ion channel regulation, calcium homeostasis and vesicular transport, such as of sorcin, stomatin, annexin A7 and RAB proteins. Cryo-electron microscopy identified two separate pathways of RBC-MV-neutrophil interaction, direct fusion with the plasma membrane and internalization, respectively. Functionally, RBC-MVs decrease neutrophil ability to phagocytose <i>Escherichia coli</i> but do not affect their survival at 24 h. This work brings new insights regarding the complexity of the RBC-MVs biogenesis, as well as their possible role in circulation.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68180606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blebs and former blebs: From surface protrusions to extracellular vesicles in cancer signalling, anoikis resistance and beyond","authors":"Dolores Di Vizio,&nbsp;Melanie Schoppet,&nbsp;Ashani Weeraratna,&nbsp;Kenneth W. Witwer","doi":"10.1002/jex2.112","DOIUrl":"https://doi.org/10.1002/jex2.112","url":null,"abstract":"<p>Associations between plasma membrane blebbing and metastatic progression have been widely reported. There are also reports of increased extracellular vesicle (EV) release from cancer cells. Yet the ties between these closely related phenomena are incompletely understood. In this commentary, we remark on a recent finding on cellular membrane blebs in melanoma signalling. We discuss possible implications for cancer biology and draw parallels to knowns and unknowns in the relationships of EVs and cancer progression.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50137942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guidelines for the purification and characterization of extracellular vesicles of parasites","authors":"Carmen Fernandez-Becerra,&nbsp;Patrícia Xander,&nbsp;Daniel Alfandari,&nbsp;George Dong,&nbsp;Iris Aparici-Herraiz,&nbsp;Irit Rosenhek-Goldian,&nbsp;Mehrdad Shokouhy,&nbsp;Melisa Gualdron-Lopez,&nbsp;Nicholy Lozano,&nbsp;Nuria Cortes-Serra,&nbsp;Paula Abou Karam,&nbsp;Paula Meneghetti,&nbsp;Rafael Pedro Madeira,&nbsp;Ziv Porat,&nbsp;Rodrigo Pedro Soares,&nbsp;Adriana Oliveira Costa,&nbsp;Sima Rafati,&nbsp;Anabela-Cordeiro da Silva,&nbsp;Nuno Santarém,&nbsp;Christopher Fernandez-Prada,&nbsp;Marcel I. Ramirez,&nbsp;Dolores Bernal,&nbsp;Antonio Marcilla,&nbsp;Vera Lucia Pereira-Chioccola,&nbsp;Lysangela Ronalte Alves,&nbsp;Hernando Del Portillo,&nbsp;Neta Regev-Rudzki,&nbsp;Igor Correia de Almeida,&nbsp;Sergio Schenkman,&nbsp;Martin Olivier,&nbsp;Ana Claudia Torrecilhas","doi":"10.1002/jex2.117","DOIUrl":"https://doi.org/10.1002/jex2.117","url":null,"abstract":"<p>Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and responsible for several millions of deaths. Research on extracellular vesicles (EVs) has increased in recent years and demonstrated that EVs shed by pathogenic parasites interact with host cells playing an important role in the parasite's survival, such as facilitation of infection, immunomodulation, parasite adaptation to the host environment and the transfer of drug resistance factors. Thus, EVs released by parasites mediate parasite-parasite and parasite-host intercellular communication. In addition, they are being explored as biomarkers of asymptomatic infections and disease prognosis after drug treatment. However, most current protocols used for the isolation, size determination, quantification and characterization of molecular cargo of EVs lack greater rigor, standardization, and adequate quality controls to certify the enrichment or purity of the ensuing bioproducts. We are now initiating major guidelines based on the evolution of collective knowledge in recent years. The main points covered in this position paper are methods for the isolation and molecular characterization of EVs obtained from parasite-infected cell cultures, experimental animals, and patients. The guideline also includes a discussion of suggested protocols and functional assays in host cells</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50137941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell culture-derived extracellular vesicles: Considerations for reporting cell culturing parameters","authors":"Faezeh Shekari,&nbsp;Faisal J. Alibhai,&nbsp;Hossein Baharvand,&nbsp;Verena Börger,&nbsp;Stefania Bruno,&nbsp;Owen Davies,&nbsp;Bernd Giebel,&nbsp;Mario Gimona,&nbsp;Ghasem Hosseini Salekdeh,&nbsp;Lorena Martin-Jaular,&nbsp;Suresh Mathivanan,&nbsp;Inge Nelissen,&nbsp;Esther Nolte-’t Hoen,&nbsp;Lorraine O'Driscoll,&nbsp;Francesca Perut,&nbsp;Stefano Pluchino,&nbsp;Gabriella Pocsfalvi,&nbsp;Carlos Salomon,&nbsp;Carolina Soekmadji,&nbsp;Simon Staubach,&nbsp;Ana Claudia Torrecilhas,&nbsp;Ganesh Vilas Shelke,&nbsp;Tobias Tertel,&nbsp;Dandan Zhu,&nbsp;Clotilde Théry,&nbsp;Kenneth Witwer,&nbsp;Rienk Nieuwland","doi":"10.1002/jex2.115","DOIUrl":"https://doi.org/10.1002/jex2.115","url":null,"abstract":"<p>Cell culture-conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing parameters affect the biochemical composition, release and possibly the function of CCM-derived EVs (CCM-EV). The CCM-EV task force of the Rigor and Standardization Subcommittee of the International Society for Extracellular Vesicles aims to identify relevant cell culturing parameters, describe their effects based on current knowledge, recommend reporting parameters and identify outstanding questions. While some recommendations are valid for all cell types, cell-specific recommendations may need to be established for non-mammalian sources, such as bacteria, yeast and plant cells. Current progress towards these goals is summarized in this perspective paper, along with a checklist to facilitate transparent reporting of cell culturing parameters to improve the reproducibility of CCM-EV research.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50135489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal isolation of extracellular vesicles from pleural fluid and profiling of their microRNA cargo","authors":"Tian Mun Chee,&nbsp;Hannah E. O'Farrell,&nbsp;Luize G. Lima,&nbsp;Andreas Möller,&nbsp;Kwun M. Fong,&nbsp;Ian A. Yang,&nbsp;Rayleen V. Bowman","doi":"10.1002/jex2.119","DOIUrl":"https://doi.org/10.1002/jex2.119","url":null,"abstract":"<p>Pleural effusion occurs in both benign and malignant pleural disease. In malignant pleural effusions, the diagnostic accuracy and sensitivity of pleural fluid cytology is less than perfect, particularly for the diagnosis of malignant pleural mesothelioma, but also in some cases for the diagnosis of metastatic pleural malignancy with primary cancer in the lung, breast or other sites. Extracellular vesicles (EVs) carry an enriched cargo of microRNAs (miRNAs) which are selectively packaged and differentially expressed in pleural disease states. To investigate the diagnostic potential of miRNA cargo in pleural fluid extracellular vesicles (PFEVs), we evaluated methods for isolating the extracellular vesicle (EV) fraction including combinations of ultracentrifugation, size-exclusion chromatography (SEC) and ultrafiltration (10 kDa filter unit). PFEVs were characterized by total and EV–associated protein, nanoparticle tracking analysis and visualisation by transmission electron microscopy. miRNA expression was analyzed by Nanostring nCounter® in separate EV fractions isolated from pleural fluid with or without additional RNA purification by ultrafiltration (3 kDa filter unit). Optimal PFEV yield, purity and miRNA expression were observed when PFEV were isolated from a larger volume of pleural fluid processed through combined ultracentrifugation and SEC techniques. Purification of total RNA by ultrafiltration further enhanced the detectability of PFEV miRNAs. This study demonstrates the feasibility of isolating PFEVs, and the potential to examine PFEV miRNA cargo using Nanostring technology to discover disease biomarkers.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50135488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between tumour and stroma modifies CLIC4 cargo in extracellular vesicles","authors":"Vanesa C. Sanchez,&nbsp;Alayna Craig-Lucas,&nbsp;Christophe Cataisson,&nbsp;Brandi L. Carofino,&nbsp;Stuart H. Yuspa","doi":"10.1002/jex2.118","DOIUrl":"https://doi.org/10.1002/jex2.118","url":null,"abstract":"<p>Mouse models of breast cancer have revealed that tumour-bearing hosts must express the oxidoreductase CLIC4 to develop lung metastases. In the absence of host CLIC4, primary tumours grow but the lung premetastatic niche is defective for metastatic seeding. Primary breast cancer cells release EVs that incorporate CLIC4 as cargo and circulate in plasma of wildtype tumour-bearing hosts. CLIC4-deficient breast cancer cells also form tumours in wildtype hosts and release EVs in plasma, but these EVs lack CLIC4, suggesting that the tumour is the source of the plasma-derived EVs that carry CLIC4 as cargo. Paradoxically, circulating EVs are also devoid of CLIC4 when CLIC4-expressing primary tumours are grown in CLIC4 knockout hosts. Thus, the incorporation of CLIC4 (and perhaps other factors) as EV cargo released from tumours involve specific signals from the surrounding stroma determined by its genetic composition. Since CLIC4 is also detected in circulating EVs from human breast cancer patients, future studies will address its association with disease.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50131922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}