Journal of Extracellular Vesicles最新文献

{"title":"Correction to abstract books","authors":"","doi":"10.1002/jev2.12503","DOIUrl":"https://doi.org/10.1002/jev2.12503","url":null,"abstract":"<p>Correction to ISEV2023 Abstract Book</p><p>(2023), ISEV2023 Abstract Book. J Extracell Vesicles., 12: e12329. https://doi.org/10.1002/jev2.12329</p><p>Correction to ISEV2024 Abstract Book</p><p>(2024), ISEV2024 Abstract Book. J Extracell Vesicles., 13: e12444. https://doi.org/10.1002/jev2.12444</p><p>In the originally published versions of these supplements, the ‘About ISEV’ section was incorrect. This has been corrected in both supplements.</p><p>We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UPCARE: Urinary Extracellular Vesicles-Derived Prostate Cancer Assessment for Risk Evaluation","authors":"Shaoqin Jiang,&nbsp;Feiting Lu,&nbsp;Jiadi Chen,&nbsp;Yingzhen Jiao,&nbsp;Qingqing Qiu,&nbsp;Xinwen Nian,&nbsp;Min Qu,&nbsp;Yan Wang,&nbsp;Mengqiang Li,&nbsp;Fei Liu,&nbsp;Xu Gao","doi":"10.1002/jev2.12491","DOIUrl":"10.1002/jev2.12491","url":null,"abstract":"<p>In the quest for efficient tumor diagnosis via liquid biopsy, extracellular vesicles (EVs) have shown promise as a source of potential biomarkers. This study addresses the gap in biomarker efficacy for predicting clinically significant prostate cancer (csPCa) between the Western and Chinese populations. We developed a urinary extracellular vesicles-based prostate score (EPS) model, utilizing the EXODUS technique for EV isolation from 598 patients and incorporating gene expressions of FOXA1, PCA3, and KLK3. Our findings reveal that the EPS model surpasses prostate-specific antigen (PSA) testing in diagnostic accuracy within a training cohort of 234 patients, achieving an area under the curve (AUC) of 0.730 compared to 0.659 for PSA (<i>p </i>= 0.018). Similarly, in a validation cohort of 101 men, the EPS model achieved an AUC of 0.749, which was significantly better than PSA's 0.577 (<i>p </i>&lt; 0.001). Our model has demonstrated a potential reduction in unnecessary prostate biopsies by 26%, with only a 3% miss rate for csPCa cases, indicating its effectiveness in the Chinese population.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12491","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roseburia intestinalis-derived extracellular vesicles ameliorate colitis by modulating intestinal barrier, microbiome, and inflammatory responses","authors":"Hwa Seung Han,&nbsp;Soonjae Hwang,&nbsp;Seung Young Choi,&nbsp;Emmanuel Hitayezu,&nbsp;Mabwi A. Humphrey,&nbsp;Altai Enkhbayar,&nbsp;Dae-Geun Song,&nbsp;Myungsuk Kim,&nbsp;Jong-Sung Park,&nbsp;Young-Tae Park,&nbsp;Jin-Soo Park,&nbsp;Kwang Hyun Cha,&nbsp;Ki Young Choi","doi":"10.1002/jev2.12487","DOIUrl":"10.1002/jev2.12487","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of <i>Roseburia intestinalis</i> (<i>R</i>)-derived EVs (R-EVs) as potent anti-inflammatory mediators in treating dextran sulfate sodium-induced colitis. <i>R</i> was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R-EVs with a 76 nm diameter were isolated from <i>R</i> using a tangential flow filtration system. Orally administered R-EVs effectively accumulated in inflamed colonic tissues and increased the abundance of <i>Bifidobacterium</i> on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile-Pro-Ile in the vesicular structure, R-EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP-1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles carry transcriptional ‘dark matter’ revealing tissue-specific information","authors":"Navneet Dogra,&nbsp;Tzu-Yi Chen,&nbsp;Edgar Gonzalez-Kozlova,&nbsp;Rebecca Miceli,&nbsp;Carlos Cordon-Cardo,&nbsp;Ashutosh K. Tewari,&nbsp;Bojan Losic,&nbsp;Gustavo Stolovitzky","doi":"10.1002/jev2.12481","DOIUrl":"10.1002/jev2.12481","url":null,"abstract":"<p>From eukaryotes to prokaryotes, all cells secrete extracellular vesicles (EVs) as part of their regular homeostasis, intercellular communication, and cargo disposal. Accumulating evidence suggests that small EVs carry functional small RNAs, potentially serving as extracellular messengers and liquid-biopsy markers. Yet, the complete transcriptomic landscape of EV-associated small RNAs during disease progression is poorly delineated due to critical limitations including the protocols used for sequencing, suboptimal alignment of short reads (20–50 nt), and uncharacterized genome annotations—often denoted as the ‘<i>dark matter</i>’ of the genome. In this study, we investigate the EV-associated small unannotated RNAs that arise from endogenous genes and are part of the genomic ‘<i>dark matter</i>’, which may play a key emerging role in regulating gene expression and translational mechanisms. To address this, we created a distinct small RNAseq dataset from human prostate cancer &amp; benign tissues, and EVs derived from blood (pre- &amp; post-prostatectomy), urine, and human prostate carcinoma epithelial cell line. We then developed an unsupervised data-based bioinformatic pipeline that recognizes biologically relevant transcriptional signals irrespective of their genomic annotation. Using this approach, we discovered distinct EV-RNA expression patterns emerging from the un-annotated genomic regions (UGRs) of the transcriptomes associated with tissue-specific phenotypes. We have named these novel EV-associated small RNAs as ‘<i>EV-UGRsʼ or “EV-dark matter”</i>. Here, we demonstrate that EV-UGR gene expressions are downregulated by ∼100 fold (FDR &lt; 0.05) in the circulating serum EVs from aggressive prostate cancer subjects. Remarkably, these EV-UGRs expression signatures were regained (upregulated) after radical prostatectomy in the same follow-up patients. Finally, we developed a stem-loop RT-qPCR assay that validated prostate cancer-specific EV-UGRs for selective fluid-based diagnostics. Overall, using an unsupervised data driven approach, we investigate the ‘<i>dark matter</i>’ of EV-transcriptome and demonstrate that EV-UGRs carry tissue-specific Information that significantly alters pre- and post-prostatectomy in the prostate cancer patients. Although further validation in randomized clinical trials is required, this new class of EV-RNAs hold promise in liquid-biopsy by avoiding highly invasive biopsy procedures in prostate cancer.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopotency and surrogate assays to validate the immunomodulatory potency of extracellular vesicles derived from mesenchymal stem/stromal cells for the treatment of experimental autoimmune uveitis","authors":"Gagandeep Kaur,&nbsp;Eun-Hye Bae,&nbsp;Yu Zhang,&nbsp;Nicole Ciacciofera,&nbsp;Kyung Min Jung,&nbsp;Heather Barreda,&nbsp;Carol Paleti,&nbsp;Joo Youn Oh,&nbsp;Ryang Hwa Lee","doi":"10.1002/jev2.12497","DOIUrl":"10.1002/jev2.12497","url":null,"abstract":"<p>Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been recognized as promising cytotherapeutics due to their demonstrated immunomodulatory effects in various preclinical models. The immunomodulatory capabilities of EVs stem from the proteins and genetic materials they carry from parent cells, but the cargo contents of EVs are significantly influenced by MSC tissues and donors, cellular age and culture conditions, resulting in functional variations. However, there are no surrogate assays available to validate the immunomodulatory potency of MSC-EVs before in vivo administration. In previous work, we discovered that microcarrier culture conditions enhance the immunomodulatory function of MSC-EVs, as well as the levels of immunosuppressive molecules such as TGF-β1 and let-7b in MSC-EVs. Building on these findings, we investigated whether TGF-β1 levels in MSC-EVs could serve as a surrogate biomarker for predicting their potency in vivo. Our studies revealed a strong correlation between TGF-β1 and let-7b levels in MSC-EVs, as well as their capacity to suppress IFN-γ secretion in stimulated splenocytes, establishing biopotency and surrogate assays for MSC-EVs. Subsequently, we validated MSC-EVs generated from monolayer cultures (ML-EVs) or microcarrier cultures (MC-EVs) using murine models of experimental autoimmune uveoretinitis (EAU) and additional in vitro assays reflecting the Mode of Action of MSC-EVs <i>in vivo</i>. Our findings demonstrated that MC-EVs carrying high levels of TGF-β1 exhibited greater efficacy than ML-EVs in halting disease progression in mice with EAU as well as inducing apoptosis and inhibiting the chemotaxis of retina-reactive T cells. Additionally, MSC-EVs suppressed the MAPK/ERK pathway in activated T cells, with treatment using TGF-β1 or let-7b showing similar effects on the MAPK/ERK pathway. Collectively, our data suggest that MSC-EVs directly inhibit the infiltration of retina-reactive T cells toward the eyes, thereby halting the disease progression in EAU mice, and their immunomodulatory potency in vivo can be predicted by their TGF-β1 levels.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of EV characterization by commercial high-sensitivity flow cytometers and a custom single-molecule flow cytometer","authors":"James Kim,&nbsp;Shihan Xu,&nbsp;Seung-Ryoung Jung,&nbsp;Alya Nguyen,&nbsp;Yuanhua Cheng,&nbsp;Mengxia Zhao,&nbsp;Bryant S. Fujimoto,&nbsp;Wyatt Nelson,&nbsp;Perry Schiro,&nbsp;Jeffrey L. Franklin,&nbsp;James N. Higginbotham,&nbsp;Robert J. Coffey,&nbsp;Min Shi,&nbsp;Lucia N. Vojtech,&nbsp;Florian Hladik,&nbsp;Muneesh Tewari,&nbsp;John Tigges,&nbsp;Ionita Ghiran,&nbsp;Tijana Jovanovic-Talisman,&nbsp;Louise C. Laurent,&nbsp;Saumya Das,&nbsp;Olesia Gololobova,&nbsp;Kenneth W. Witwer,&nbsp;Tuoye Xu,&nbsp;Al Charest,&nbsp;Kendall Van Keuren Jensen,&nbsp;Robert L. Raffai,&nbsp;Jennifer C. Jones,&nbsp;Joshua A. Welsh,&nbsp;John P. Nolan,&nbsp;Daniel T. Chiu","doi":"10.1002/jev2.12498","DOIUrl":"10.1002/jev2.12498","url":null,"abstract":"<p>High-sensitivity flow cytometers have been developed for multi-parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the characterization of identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high-sensitivity flow cytometers, two commercial instruments, CytoFLEX/CellStream, and a custom single-molecule flow cytometer (SMFC). DiFi EVs were stained with the membrane dye di-8-ANEPPS and with PE-conjugated anti-EGFR or anti-tetraspanin (CD9/CD63/CD81) antibodies for estimation of EV size and surface protein copy numbers. The limits of detection (LODs) for immunofluorescence and vesicle size based on calibration using cross-calibrated, hard-dyed beads were ∼10 PE/∼80 nm EV diameter for CytoFLEX and ∼10 PEs/∼67 nm for CellStream. For the SMFC, the LOD for immunofluorescence was 1 PE and ≤ 35 nm for size. The population of EVs detected by each system (di-8-ANEPPS⁺/PE⁺ particles) differed widely depending on the LOD of the system; for example, CellStream/CytoFLEX detected only 5.7% and 1.5% of the tetraspanin-labelled EVs detected by SMFC, respectively, and median EV diameter and antibody copy numbers were much larger for CellStream/CytoFLEX than for SMFC as measured and validated using super-resolution/single-molecule TIRF microscopy. To obtain a dataset representing a common EV population analysed by all three platforms, we filtered out SMFC and CellStream measurements for EVs below the CytoFLEX LODs as determined by bead calibration (10 PE/80 nm). The inter-platform agreement using this filtered dataset was significantly better than for the unfiltered dataset, but even better concordance between results was obtained by applying higher cutoffs (21 PE/120 nm) determined by threshold analysis using the SMFC data. The results demonstrate the impact of specifying LODs to define the EV population analysed on inter-instrument reproducibility in EV flow cytometry studies, and the utility of threshold analysis of SMFC data for providing semi-quantitative LOD values for other flow cytometers.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of extracellular vesicles in the pathogenesis, diagnosis and therapy for parasitic diseases","authors":"Ana Acacia Sá Pinheiro,&nbsp;Ana Claudia Torrecilhas,&nbsp;Bruno Solano de Freitas Souza,&nbsp;Fernanda Ferreira Cruz,&nbsp;Herbert Leonel de Matos Guedes,&nbsp;Tadeu Diniz Ramos,&nbsp;Miqueias Lopes-Pacheco,&nbsp;Celso Caruso-Neves,&nbsp;Patricia R. M. Rocco","doi":"10.1002/jev2.12496","DOIUrl":"10.1002/jev2.12496","url":null,"abstract":"<p>Parasitic diseases have a significant impact on human and animal health, representing a major hazard to the public and causing economic and health damage worldwide. Extracellular vesicles (EVs) have long been recognized as diagnostic and therapeutic tools but are now also known to be implicated in the natural history of parasitic diseases and host immune response modulation. Studies have shown that EVs play a role in parasitic disease development by interacting with parasites and communicating with other types of cells. This review highlights the most recent research on EVs and their role in several aspects of parasite-host interactions in five key parasitic diseases: Chagas disease, malaria, toxoplasmosis, leishmaniasis and helminthiases. We also discuss the potential use of EVs as diagnostic tools or treatment options for these infectious diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles miR-31-5p promotes pancreatic cancer chemoresistance via regulating LATS2-Hippo pathway and promoting SPARC secretion from pancreatic stellate cells","authors":"Cheng Qin,&nbsp;Bangbo Zhao,&nbsp;Yuanyang Wang,&nbsp;Zeru Li,&nbsp;Tianyu Li,&nbsp;Yutong Zhao,&nbsp;Weibin Wang,&nbsp;Yupei Zhao","doi":"10.1002/jev2.12488","DOIUrl":"10.1002/jev2.12488","url":null,"abstract":"<p>Pancreatic cancer remains one of the most lethal malignant diseases. Gemcitabine-based chemotherapy is still one of the first-line systemic treatments, but chemoresistance occurs in the majority of patients. Recently, accumulated evidence has demonstrated the role of the tumour microenvironment in promoting chemoresistance. In the tumour microenvironment, pancreatic stellate cells (PSCs) are among the main cellular components, and extracellular vesicles (EVs) are common mediators of cell‒cell communication. In this study, we showed that SP1-transcribed miR-31-5p not only targeted LATS2 in pancreatic cancer cells but also regulated the Hippo pathway in PSCs through EV transfer. Consequently, PSCs synthesized and secreted protein acidic and rich in cysteins (SPARC), which was preferentially expressed in stromal cells, stimulating Extracellular Signal regulated kinase (ERK) signalling in pancreatic cancer cells. Therefore, pancreatic cancer cell survival and chemoresistance were improved due to both the intrinsic Hippo pathway regulated by miR-31-5p and external SPARC-induced ERK signalling. In mouse models, miR-31-5p overexpression in pancreatic cancer cells promoted the chemoresistance of coinjected xenografts. In a tissue microarray, pancreatic cancer patients with higher miR-31-5p expression had shorter overall survival. Therefore, miR-31-5p regulates the Hippo pathway in multiple cell types within the tumour microenvironment via EVs, ultimately contributing to the chemoresistance of pancreatic cancer cells.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Predictive Model for Initial Platinum-Based Chemotherapy Efficacy in Patients with Postoperative Epithelial Ovarian Cancer Using Tissue-Derived Small Extracellular Vesicles","authors":"Shizhen Shen,&nbsp;Conghui Wang,&nbsp;Jiaxin Gu,&nbsp;Feifei Song,&nbsp;Xiaodong Wu,&nbsp;Fangfang Qian,&nbsp;Xiaojing Chen,&nbsp;Lingfang Wang,&nbsp;Qiaohua Peng,&nbsp;Ziyu Xing,&nbsp;Lingkai Gu,&nbsp;Fenfen Wang,&nbsp;Xiaodong Cheng","doi":"10.1002/jev2.12486","DOIUrl":"10.1002/jev2.12486","url":null,"abstract":"<p>Epithelial ovarian cancer (EOC) is an often-fatal malignancy marked by the development of resistance to platinum-based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue-derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data-independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum-sensitive and 30 platinum-resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune-related pathways. Moreover, pivotal immune-related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum-based chemotherapy in patients with EOC post-surgery, providing prognostic insights even before the initiation of chemotherapy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of the αVβ3 integrin affects prostate cancer sEV cargo and density and promotes sEV pro-tumorigenic activity in vivo through a GPI-anchored receptor, NgR2","authors":"Cecilia E. Verrillo,&nbsp;Fabio Quaglia,&nbsp;Christopher D. Shields,&nbsp;Stephen Lin,&nbsp;Andrew V. Kossenkov,&nbsp;Hsin-Yao Tang,&nbsp;David Speicher,&nbsp;Nicole M. Naranjo,&nbsp;Anna Testa,&nbsp;William K. Kelly,&nbsp;Qin Liu,&nbsp;Benjamin Leiby,&nbsp;Luca Musante,&nbsp;Khalid Sossey-Alaoui,&nbsp;Navneet Dogra,&nbsp;Tzu-Yi Chen,&nbsp;Dario C. Altieri,&nbsp;Lucia R. Languino","doi":"10.1002/jev2.12482","DOIUrl":"10.1002/jev2.12482","url":null,"abstract":"<p>It is known that small extracellular vesicles (sEVs) are released from cancer cells and contribute to cancer progression via crosstalk with recipient cells. We have previously reported that sEVs expressing the αVβ3 integrin, a protein upregulated in aggressive neuroendocrine prostate cancer (NEPrCa), contribute to neuroendocrine differentiation (NED) in recipient cells. Here, we examine the impact of αVβ3 expression on sEV protein content, density and function. sEVs used in this study were isolated by iodixanol density gradients and characterized by nanoparticle tracking analysis, immunoblotting and single vesicle analysis. Our proteomic profile of sEVs containing αVβ3 shows downregulation of typical effectors involved in apoptosis and necrosis and an upregulation of tumour cell survival factors compared to control sEVs. We also show that the expression of αVβ3 in sEVs causes a distinct reposition of EV markers (Alix, CD81, CD9) to a low-density sEV subpopulation. This low-density reposition is independent of extracellular matrix (ECM) protein interactions with sEVs. This sEV subset contains αVβ3 and an αVβ3 downstream effector, NgR2, a novel marker for NEPrCa. We show that sEVs containing αVβ3 are loaded with higher amounts of NgR2 as compared to sEVs that do not express αVβ3. Mechanistically, we demonstrate that sEVs containing NgR2 do not affect the sEV marker profile, but when injected in vivo intratumorally, they promote tumour growth and induce NED. We show that sEVs expressing NgR2 increase the activation of focal adhesion kinase (FAK), a known promoter of cancer cell proliferation, in recipient cells. We also show that NgR2 mimics the effect of sEVs containing αVβ3 since it displays increased growth of NgR2 transfectants in vivo, as compared to control cells. Overall, our results describe the changes that occur in cargo, density and functions of cancer cell-derived sEVs containing the αVβ3 integrin and its effector, NgR2, without affecting the sEV tetraspanin profiles.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"13 8","pages":""},"PeriodicalIF":15.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}