Jose Manuel Sanchez-Manas, Natalia Perez de Gracia, S. Perales, Joaquina Martínez-Galán, Carolina Torres, Pedro J. Real
Pancreatic cancer is a highly lethal and metastatic malignancy, mainly because it often remains undetected until advanced stages due to the limitations of current diagnostic methods, rendering currently available therapies ineffective. Therefore, it is imperative to identify useful biomarkers for early diagnosis and new therapeutic targets for pancreatic cancer. Recently, extracellular vesicles have emerged as promising biomarkers for the diagnosis and prognosis of pancreatic cancer. Given their presence in various bodily fluids, extracellular vesicles offer a non-invasive approach through liquid biopsy to detect and monitor cancer progression. In this review, we comprehensively examine the multifaceted roles of extracellular vesicles in the progression of cancer, while also exploring their potential as diagnostic, prognostic, and therapeutic biomarkers in the context of pancreatic cancer.
{"title":"Potential clinical applications of extracellular vesicles in pancreatic cancer: exploring untapped opportunities from biomarkers to novel therapeutic approaches","authors":"Jose Manuel Sanchez-Manas, Natalia Perez de Gracia, S. Perales, Joaquina Martínez-Galán, Carolina Torres, Pedro J. Real","doi":"10.20517/evcna.2023.68","DOIUrl":"https://doi.org/10.20517/evcna.2023.68","url":null,"abstract":"Pancreatic cancer is a highly lethal and metastatic malignancy, mainly because it often remains undetected until advanced stages due to the limitations of current diagnostic methods, rendering currently available therapies ineffective. Therefore, it is imperative to identify useful biomarkers for early diagnosis and new therapeutic targets for pancreatic cancer. Recently, extracellular vesicles have emerged as promising biomarkers for the diagnosis and prognosis of pancreatic cancer. Given their presence in various bodily fluids, extracellular vesicles offer a non-invasive approach through liquid biopsy to detect and monitor cancer progression. In this review, we comprehensively examine the multifaceted roles of extracellular vesicles in the progression of cancer, while also exploring their potential as diagnostic, prognostic, and therapeutic biomarkers in the context of pancreatic cancer.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":" 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Mitchell, I. Ben-Dov, Christina Liu, Tao Wang, Rachel B. Hazan, Thomas L. Bauer, Johannes Zakrzewski, Kathryn Donnelly, Kar Chow, Junfeng Ma, Olivier Loudig
Aim: The lung is the second most frequent site of metastatic dissemination. Early detection is key to improving survival. Given that the lung interfaces with the external environment, the collection of exhaled breath condensate (EBC) provides the opportunity to obtain biological material including exhaled miRNAs that originate from the lung. Methods: In this proof-of-principal study, we used the highly metastatic MDA-MB-231 subline 3475 breast cancer cell line (LM-3475) to establish an orthotopic lung tumor-bearing mouse model and investigate non-invasive detection of lung tumors by analysis of exhaled miRNAs. We initially conducted miRNA NGS and qPCR validation analyses on condensates collected from unrestrained animals and identified significant miRNA expression differences between the condensates of lung tumor-bearing and control mice. To focus our purification of EBC and evaluate the origin of these differentially expressed miRNAs, we developed a system to collect EBC directly from the nose and mouth of our mice. Results: Using nanoparticle distribution analyses, TEM, and ONi super-resolution nanoimaging, we determined that human tumor EVs could be increasingly detected in mouse EBC during the progression of secondary lung tumors. Using our customizable EV-CATCHER assay, we purified human tumor EVs from mouse EBC and demonstrated that the bulk of differentially expressed exhaled miRNAs originate from lung tumors, which could be detected by qPCR within 1 to 2 weeks after tail vein injection of the metastatic cells. Conclusion: This study is the first of its kind and demonstrates that lung tumor EVs are exhaled in mice and provide non-invasive biomarkers for detection of lung tumors.
{"title":"Non-invasive detection of orthotopic human lung tumors by microRNA expression profiling of mouse exhaled breath condensates and exhaled extracellular vesicles","authors":"M. Mitchell, I. Ben-Dov, Christina Liu, Tao Wang, Rachel B. Hazan, Thomas L. Bauer, Johannes Zakrzewski, Kathryn Donnelly, Kar Chow, Junfeng Ma, Olivier Loudig","doi":"10.20517/evcna.2023.77","DOIUrl":"https://doi.org/10.20517/evcna.2023.77","url":null,"abstract":"Aim: The lung is the second most frequent site of metastatic dissemination. Early detection is key to improving survival. Given that the lung interfaces with the external environment, the collection of exhaled breath condensate (EBC) provides the opportunity to obtain biological material including exhaled miRNAs that originate from the lung.\u0000 Methods: In this proof-of-principal study, we used the highly metastatic MDA-MB-231 subline 3475 breast cancer cell line (LM-3475) to establish an orthotopic lung tumor-bearing mouse model and investigate non-invasive detection of lung tumors by analysis of exhaled miRNAs. We initially conducted miRNA NGS and qPCR validation analyses on condensates collected from unrestrained animals and identified significant miRNA expression differences between the condensates of lung tumor-bearing and control mice. To focus our purification of EBC and evaluate the origin of these differentially expressed miRNAs, we developed a system to collect EBC directly from the nose and mouth of our mice.\u0000 Results: Using nanoparticle distribution analyses, TEM, and ONi super-resolution nanoimaging, we determined that human tumor EVs could be increasingly detected in mouse EBC during the progression of secondary lung tumors. Using our customizable EV-CATCHER assay, we purified human tumor EVs from mouse EBC and demonstrated that the bulk of differentially expressed exhaled miRNAs originate from lung tumors, which could be detected by qPCR within 1 to 2 weeks after tail vein injection of the metastatic cells.\u0000 Conclusion: This study is the first of its kind and demonstrates that lung tumor EVs are exhaled in mice and provide non-invasive biomarkers for detection of lung tumors.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"44 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140368240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This commentary provides an in-depth analysis and perspective on the pioneering research article titled ‘Extracellular Vesicle-Encapsulated Adeno-Associated Viruses for Therapeutic Gene Delivery to the Heart’. The original study explores the innovative use of extracellular vesicle-encapsulated AAVs (EV-AAV-6 and -9) as a superior gene-delivery approach for cardiomyocytes (CMs), which not only provides increased AAV neutralizing antibody (NAb) resistance but also has implications for increased gene delivery efficacy to ischemic hearts. This study examined the efficacy of EVs isolated from the conditioned medium of AAV-6 and -9 producing HEK293T cells in combinatorial in vitro and in vivo model systems in comparison to free AAVs in the presence of the NAbs. This commentary highlights the key findings, discusses potential implications, limitations, and suggests future directions for research in this evolving field.
{"title":"Gene therapy for the heart: encapsulated viruses to the rescue","authors":"Uma Maheswari Deshetty, S. Sil, Shilpa Buch","doi":"10.20517/evcna.2023.70","DOIUrl":"https://doi.org/10.20517/evcna.2023.70","url":null,"abstract":"This commentary provides an in-depth analysis and perspective on the pioneering research article titled ‘Extracellular Vesicle-Encapsulated Adeno-Associated Viruses for Therapeutic Gene Delivery to the Heart’. The original study explores the innovative use of extracellular vesicle-encapsulated AAVs (EV-AAV-6 and -9) as a superior gene-delivery approach for cardiomyocytes (CMs), which not only provides increased AAV neutralizing antibody (NAb) resistance but also has implications for increased gene delivery efficacy to ischemic hearts. This study examined the efficacy of EVs isolated from the conditioned medium of AAV-6 and -9 producing HEK293T cells in combinatorial in vitro and in vivo model systems in comparison to free AAVs in the presence of the NAbs. This commentary highlights the key findings, discusses potential implications, limitations, and suggests future directions for research in this evolving field.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"22 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140430016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mia S. C. Yu, Tanja V. Edelbacher, C. Grätz, D. Chiang, M. Reithmair, M. Pfaffl
{"title":"Summary report of the 1st MOVE symposium in Málaga from 24-27th October 2023 - Foster the European mobility for young scientists in extracellular vesicles research","authors":"Mia S. C. Yu, Tanja V. Edelbacher, C. Grätz, D. Chiang, M. Reithmair, M. Pfaffl","doi":"10.20517/evcna.2024.09","DOIUrl":"https://doi.org/10.20517/evcna.2024.09","url":null,"abstract":"","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140430498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell membrane-derived vesicles (CMVs) are particles generated from living cells, including extracellular vesicles (EVs) and artificial extracellular vesicles (aEVs) prepared from cell membranes. CMVs possess considerable potential in drug delivery, regenerative medicine, immunomodulation, disease diagnosis, etc . owing to their stable lipid bilayer structure, favorable biocompatibility, and low toxicity. Although the majority of CMVs inherit certain attributes from the original cells, it is still difficult to execute distinct therapeutic functions, such as organ targeting, signal regulation, and exogenous biotherapeutic supplementation. Hence, engineering CMVs by genetic engineering, chemical modification, and hybridization is a promising way to endow CMVs with specific functions and open up novel vistas for applications. In particular, there is a growing interest in genetically engineered CMVs harnessed to exhibit biotherapeutics. Herein, we outline the preparation strategies and their characteristics for purifying CMVs. Additionally, we review the advances of genetically engineered CMVs utilized to target organs, regulate signal transduction, and deliver biomacromolecules and chemical drugs. Furthermore, we also summarize the emerging therapeutic applications of genetically engineered CMVs in addressing tumors, diabetes, systemic lupus erythematosus, and cardiovascular diseases.
{"title":"Harnessing genetically engineered cell membrane-derived vesicles as biotherapeutics","authors":"Xiaohong Li, Yuting Wei, Zhirang Zhang, Xudong Zhang","doi":"10.20517/evcna.2023.58","DOIUrl":"https://doi.org/10.20517/evcna.2023.58","url":null,"abstract":"Cell membrane-derived vesicles (CMVs) are particles generated from living cells, including extracellular vesicles (EVs) and artificial extracellular vesicles (aEVs) prepared from cell membranes. CMVs possess considerable potential in drug delivery, regenerative medicine, immunomodulation, disease diagnosis, etc . owing to their stable lipid bilayer structure, favorable biocompatibility, and low toxicity. Although the majority of CMVs inherit certain attributes from the original cells, it is still difficult to execute distinct therapeutic functions, such as organ targeting, signal regulation, and exogenous biotherapeutic supplementation. Hence, engineering CMVs by genetic engineering, chemical modification, and hybridization is a promising way to endow CMVs with specific functions and open up novel vistas for applications. In particular, there is a growing interest in genetically engineered CMVs harnessed to exhibit biotherapeutics. Herein, we outline the preparation strategies and their characteristics for purifying CMVs. Additionally, we review the advances of genetically engineered CMVs utilized to target organs, regulate signal transduction, and deliver biomacromolecules and chemical drugs. Furthermore, we also summarize the emerging therapeutic applications of genetically engineered CMVs in addressing tumors, diabetes, systemic lupus erythematosus, and cardiovascular diseases.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"72 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140482483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cirrhotic patients can present hepatic encephalopathy (HE), showing motor and cognitive deficits. Hyperammonemia and peripheral inflammation are known to induce neuroinflammation and alter neurotransmission, which finally induces neurological impairment in HE. However, the mechanisms by which the deleterious effects of peripheral inflammation are transmitted to the brain are not well understood. Extracellular vesicles (EVs) have recently emerged as a new mediator between the periphery and the brain, particularly in pathologies associated with sustained inflammation and in neurological disorders. In this work, we summarized the main findings on the role of plasma EVs in hyperammonemia and HE and discussed its potential implication in the pathogenesis of hepatic encephalopathy.
{"title":"Contribution of extracellular vesicles to neuroinflammation and cognitive and motor deficits in hyperammonemia and hepatic encephalopathy","authors":"Paula Izquierdo-Altarejos, Vicente Felipo","doi":"10.20517/evcna.2023.66","DOIUrl":"https://doi.org/10.20517/evcna.2023.66","url":null,"abstract":"Cirrhotic patients can present hepatic encephalopathy (HE), showing motor and cognitive deficits. Hyperammonemia and peripheral inflammation are known to induce neuroinflammation and alter neurotransmission, which finally induces neurological impairment in HE. However, the mechanisms by which the deleterious effects of peripheral inflammation are transmitted to the brain are not well understood. Extracellular vesicles (EVs) have recently emerged as a new mediator between the periphery and the brain, particularly in pathologies associated with sustained inflammation and in neurological disorders. In this work, we summarized the main findings on the role of plasma EVs in hyperammonemia and HE and discussed its potential implication in the pathogenesis of hepatic encephalopathy.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"113 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139616335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angelica Ortiz, Aikaterini Stavrou, Shan Liu, Danqi Chen, Steven S. Shen, Chunyuan Jin
Aim: This study aims to elucidate the involvement of triple-negative breast cancer (TNBC)-derived extracellular vesicles in metastasis. The loss of components in the type 1 interferon (IFN1) signaling pathway has been linked to the promotion of metastasis. However, IFN1 signaling induces immunological dormancy and promotes tumorigenesis. Our hypothesis was that TNBC cells release tumor-derived extracellular vesicles (TEVs) that promote metastasis in an IFN1-independent manner. Methods: Two murine TNBC models and transgenic mice were used to examine the role of IFN1 in TNBC progression to metastasis. Reserpine was employed to determine the effect of TEV education on TNBC progression and overall survival. EVs from cancer cells treated with vehicle and reserpine and from the serum of tumor-bearing mice receiving reserpine were examined to determine changes in EV release and EV content. Results: TNBC cells progress to metastasis in mice lacking the IFN1-induced gene cholesterol-25 hydroxylase (CH25H) or expressing the IFNAR1S526 knock-in that cannot be downregulated. Reserpine suppresses EV release from TNBC cells in vitro and in vivo . Western blot analysis demonstrated reserpine decreased NUPR1 protein levels in EVs. RNAseq analysis demonstrated that endothelial cells lacking CH25H treated with TEVs exhibited increased NUPR1 expression that was decreased by adding reserpine with the TEVs. NUPR1 overexpression upregulated genes that mediate TEV biogenesis and incorporation. Knockdown of NUPR1 with shRNA decreased the release of TEVs. Conclusion: In conclusion, our study suggests that TNBC is driven by aberrant packaging of NUPR1 into TEVs which were transferred into recipient cells to activate pro-metastatic transcription driven by NUPR1.
目的：本研究旨在阐明三阴性乳腺癌（TNBC）产生的细胞外囊泡参与转移的情况。1型干扰素（IFN1）信号通路中成分的缺失与促进转移有关。然而，IFN1 信号诱导免疫休眠并促进肿瘤发生。我们的假设是，TNBC细胞释放的肿瘤衍生胞外囊泡（TEVs）会以不依赖IFN1的方式促进转移。研究方法使用两种小鼠 TNBC 模型和转基因小鼠来研究 IFN1 在 TNBC 转移过程中的作用。采用瑞瑟平确定 TEV 教育对 TNBC 进展和总生存期的影响。研究人员检测了用载体和利舍平处理的癌细胞中的EV，以及接受利舍平治疗的肿瘤小鼠血清中的EV，以确定EV释放和EV含量的变化。结果TNBC细胞在缺乏IFN1诱导基因胆固醇-25羟化酶（CH25H）或表达无法被下调的IFNAR1S526基因敲入的小鼠体内发生转移。Reserpine 可抑制 TNBC 细胞在体外和体内的 EV 释放。Western 印迹分析表明，利舍平降低了 EV 中的 NUPR1 蛋白水平。RNAseq 分析表明，用 TEVs 处理缺乏 CH25H 的内皮细胞会增加 NUPR1 的表达，而在 TEVs 中添加瑞舍平可降低 NUPR1 的表达。NUPR1 的过表达上调了介导 TEV 生物发生和整合的基因。用 shRNA 敲除 NUPR1 可减少 TEV 的释放。结论总之，我们的研究表明，TNBC是由NUPR1异常包装成TEVs驱动的，TEVs被转移到受体细胞中，激活由NUPR1驱动的促转移转录。
{"title":"NUPR1 packaged in extracellular vesicles promotes murine triple-negative breast cancer in a type 1 interferon-independent manner","authors":"Angelica Ortiz, Aikaterini Stavrou, Shan Liu, Danqi Chen, Steven S. Shen, Chunyuan Jin","doi":"10.20517/evcna.2023.59","DOIUrl":"https://doi.org/10.20517/evcna.2023.59","url":null,"abstract":"Aim: This study aims to elucidate the involvement of triple-negative breast cancer (TNBC)-derived extracellular vesicles in metastasis. The loss of components in the type 1 interferon (IFN1) signaling pathway has been linked to the promotion of metastasis. However, IFN1 signaling induces immunological dormancy and promotes tumorigenesis. Our hypothesis was that TNBC cells release tumor-derived extracellular vesicles (TEVs) that promote metastasis in an IFN1-independent manner.\u0000 Methods: Two murine TNBC models and transgenic mice were used to examine the role of IFN1 in TNBC progression to metastasis. Reserpine was employed to determine the effect of TEV education on TNBC progression and overall survival. EVs from cancer cells treated with vehicle and reserpine and from the serum of tumor-bearing mice receiving reserpine were examined to determine changes in EV release and EV content.\u0000 Results: TNBC cells progress to metastasis in mice lacking the IFN1-induced gene cholesterol-25 hydroxylase (CH25H) or expressing the IFNAR1S526 knock-in that cannot be downregulated. Reserpine suppresses EV release from TNBC cells in vitro and in vivo . Western blot analysis demonstrated reserpine decreased NUPR1 protein levels in EVs. RNAseq analysis demonstrated that endothelial cells lacking CH25H treated with TEVs exhibited increased NUPR1 expression that was decreased by adding reserpine with the TEVs. NUPR1 overexpression upregulated genes that mediate TEV biogenesis and incorporation. Knockdown of NUPR1 with shRNA decreased the release of TEVs.\u0000 Conclusion: In conclusion, our study suggests that TNBC is driven by aberrant packaging of NUPR1 into TEVs which were transferred into recipient cells to activate pro-metastatic transcription driven by NUPR1.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":" 57","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139618973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simona Di Giulio, E. Carata, Marco Muci, S. Mariano, E. Panzarini
Hypoxia is a pathologic condition characterized by a tissue oxygen deficiency due to either decreased oxygen intake from outside and/or disruption of oxygen utilization in cells. This condition may arise when the oxygen demand exceeds its supply or the partial pressure of oxygen is below 10 mmHg. This situation poses a significant problem for glioblastoma (GBM) patients as it can activate angiogenesis, increase invasiveness and metastatic risk, prolong tumor survival, and suppress anti-tumor immunity, making hypoxic cells resistant to radiotherapy and chemotherapy. Low oxygen levels in tumors can cause severe cellular changes that can affect the release of extracellular vesicles (EVs), especially exosomes (EXOs), altering their proteomic profile both qualitatively and quantitatively. EXOs represent an adaptive response to hypoxic stress; therefore, they can be used to determine oxygen levels in cancer and assess its aggressiveness. They not only release signaling molecules to attract cells that promote the formation of small vessel walls but also send signals to other tumor cells that trigger their migration, which in turn plays a crucial role in the formation of metastases under hypoxia. This review investigates how the molecular profile of GBM-derived exosomes changes under hypoxic conditions, offering future possibilities for noninvasive diagnosis and monitoring of brain tumor patients.
{"title":"Impact of hypoxia on the molecular content of glioblastoma-derived exosomes","authors":"Simona Di Giulio, E. Carata, Marco Muci, S. Mariano, E. Panzarini","doi":"10.20517/evcna.2023.52","DOIUrl":"https://doi.org/10.20517/evcna.2023.52","url":null,"abstract":"Hypoxia is a pathologic condition characterized by a tissue oxygen deficiency due to either decreased oxygen intake from outside and/or disruption of oxygen utilization in cells. This condition may arise when the oxygen demand exceeds its supply or the partial pressure of oxygen is below 10 mmHg. This situation poses a significant problem for glioblastoma (GBM) patients as it can activate angiogenesis, increase invasiveness and metastatic risk, prolong tumor survival, and suppress anti-tumor immunity, making hypoxic cells resistant to radiotherapy and chemotherapy. Low oxygen levels in tumors can cause severe cellular changes that can affect the release of extracellular vesicles (EVs), especially exosomes (EXOs), altering their proteomic profile both qualitatively and quantitatively. EXOs represent an adaptive response to hypoxic stress; therefore, they can be used to determine oxygen levels in cancer and assess its aggressiveness. They not only release signaling molecules to attract cells that promote the formation of small vessel walls but also send signals to other tumor cells that trigger their migration, which in turn plays a crucial role in the formation of metastases under hypoxia. This review investigates how the molecular profile of GBM-derived exosomes changes under hypoxic conditions, offering future possibilities for noninvasive diagnosis and monitoring of brain tumor patients.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":" 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139625929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chun Liu, C. Seneviratne, Carlos Palma, Greg Rice, Carlos Salomon, Ramin Khanabdali, S. Ivanovski, Pingping Han
Aim: Saliva extracellular vesicles (EVs) serve as a significant reservoir of biomarkers that may be of clinical use in disease diagnosis. Saliva, however, contains EVs of both host- and bacterial- origin. Identifying suitable EVs for disease diagnosis involves enriching host EVs and limiting non-host contamination with effective isolation methods. The objectives of this research were: (1) to evaluate the salivary EVs enrichment in 12 periodontally healthy patients by two different methods: size exclusion chromatography (SEC) and bead-based immunoaffinity capture (EXO-NET®); (2) to analyze the variance expression of inflammatory cytokines in EXO-NET-enriched EVs, comparing individuals with periodontitis (n = 20) to non-periodontitis (n = 12). Methods: Whole unstimulated saliva samples were collected from 12 periodontally healthy and 20 periodontitis patients. EVs were isolated from the 12 non-periodontitis patients using SEC (referred to as SEC-EVs) and EXO-NET (referred to as EXO-NET EVs), after which their total protein content, 37 EV surface markers, and bacterial pathogens expression were compared. Subsequently, the inflammatory cytokines expression levels (interleukin-IL-6, IL-1β, IL-8, and IL-10) in EXO-NET EVs were measured for non-periodontitis and periodontitis. Results: EXO-NET EVs contained more EV-specific protein and substantially higher expression of EV surface markers (CD9, CD81, CD63), but less pathogenic DNA was detected compared to that in SEC-EVs. Additionally, EXO-NET EVs from periodontitis patients contained higher amounts of IL-6 and IL-8, and decreased IL-10, compared to those from non-periodontitis patients. Conclusion: The findings suggest that immunoaffinity capture (EXO-NET) is a dependable method for salivary EVs enrichment, resulting in a higher yield of host EVs with reduced bacterial DNA detection compared to SEC. Furthermore, the research proposes that immunoaffinity capture enriched EVs can function as biomarkers for periodontitis, demonstrated by an increased expression of proinflammatory cytokines from periodontitis patients.
{"title":"Immunoaffinity-enriched salivary small extracellular vesicles in periodontitis","authors":"Chun Liu, C. Seneviratne, Carlos Palma, Greg Rice, Carlos Salomon, Ramin Khanabdali, S. Ivanovski, Pingping Han","doi":"10.20517/evcna.2023.48","DOIUrl":"https://doi.org/10.20517/evcna.2023.48","url":null,"abstract":"Aim: Saliva extracellular vesicles (EVs) serve as a significant reservoir of biomarkers that may be of clinical use in disease diagnosis. Saliva, however, contains EVs of both host- and bacterial- origin. Identifying suitable EVs for disease diagnosis involves enriching host EVs and limiting non-host contamination with effective isolation methods. The objectives of this research were: (1) to evaluate the salivary EVs enrichment in 12 periodontally healthy patients by two different methods: size exclusion chromatography (SEC) and bead-based immunoaffinity capture (EXO-NET®); (2) to analyze the variance expression of inflammatory cytokines in EXO-NET-enriched EVs, comparing individuals with periodontitis (n = 20) to non-periodontitis (n = 12). Methods: Whole unstimulated saliva samples were collected from 12 periodontally healthy and 20 periodontitis patients. EVs were isolated from the 12 non-periodontitis patients using SEC (referred to as SEC-EVs) and EXO-NET (referred to as EXO-NET EVs), after which their total protein content, 37 EV surface markers, and bacterial pathogens expression were compared. Subsequently, the inflammatory cytokines expression levels (interleukin-IL-6, IL-1β, IL-8, and IL-10) in EXO-NET EVs were measured for non-periodontitis and periodontitis. Results: EXO-NET EVs contained more EV-specific protein and substantially higher expression of EV surface markers (CD9, CD81, CD63), but less pathogenic DNA was detected compared to that in SEC-EVs. Additionally, EXO-NET EVs from periodontitis patients contained higher amounts of IL-6 and IL-8, and decreased IL-10, compared to those from non-periodontitis patients. Conclusion: The findings suggest that immunoaffinity capture (EXO-NET) is a dependable method for salivary EVs enrichment, resulting in a higher yield of host EVs with reduced bacterial DNA detection compared to SEC. Furthermore, the research proposes that immunoaffinity capture enriched EVs can function as biomarkers for periodontitis, demonstrated by an increased expression of proinflammatory cytokines from periodontitis patients.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":" 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139141930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells have the capability to discharge extracellular vesicles (EVs) into a range of bodily fluids. Extracellular vesicles (EVs) encapsulate biological molecules such as proteins and nucleic acids, playing a role in facilitating cell-cell communication. They actively engage in a myriad of physiological and pathological processes. In vivo tracing of EVs in organisms significantly contributes to elucidating the biological mechanisms of EV-based therapy. The development of molecular imaging technology makes it possible to trace EVs in vivo . Experiments frequently employ a range of molecular imaging techniques, encompassing bioluminescence imaging, fluorescence imaging, magnetic resonance imaging, single photon emission computed tomography, positron emission tomography, photoacoustic imaging, and multimodal imaging. These methods have their own advantages and disadvantages. In this review, typical applications of in vivo tracing of EVs are reviewed.
{"title":"Research progress in in vivo tracing technology for extracellular vesicles","authors":"Yanhua Shi, Xianghui Wang, Shifang Zhang, Hao Yin, Huaju Fan, Yaohui Tang, Nana Yang","doi":"10.20517/evcna.2023.49","DOIUrl":"https://doi.org/10.20517/evcna.2023.49","url":null,"abstract":"Cells have the capability to discharge extracellular vesicles (EVs) into a range of bodily fluids. Extracellular vesicles (EVs) encapsulate biological molecules such as proteins and nucleic acids, playing a role in facilitating cell-cell communication. They actively engage in a myriad of physiological and pathological processes. In vivo tracing of EVs in organisms significantly contributes to elucidating the biological mechanisms of EV-based therapy. The development of molecular imaging technology makes it possible to trace EVs in vivo . Experiments frequently employ a range of molecular imaging techniques, encompassing bioluminescence imaging, fluorescence imaging, magnetic resonance imaging, single photon emission computed tomography, positron emission tomography, photoacoustic imaging, and multimodal imaging. These methods have their own advantages and disadvantages. In this review, typical applications of in vivo tracing of EVs are reviewed.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138597879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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