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Extracellular vesicles: Emerging mediators of cell communication in gastrointestinal cancers exhibiting metabolic abnormalities 细胞外小泡:表现出代谢异常的胃肠道癌症中新出现的细胞通讯介质。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.08.001
Ghazaleh Pourali , Nima Zafari , Hamid Fiuji , Jyotsna Batra , Elham Nazari , Majid Khazaei , Seyed Mahdi Hassanian , Mahrou Vahabi , MohammadAli Kiani , Majid Ghayour-Mobarhan , Godefridus J. Peters , Gordon A. Ferns , Alfred King-yin Lam , Elisa Giovannetti , Amir Avan

There is a complex interaction between pro-tumoural and anti-tumoural networks in the tumour microenvironment (TME). Throughout tumourigenesis, communication between malignant cells and various cells of the TME contributes to metabolic reprogramming. Tumour Dysregulation of metabolic pathways offer an evolutional advantage in the TME and enhance the tumour progression, invasiveness, and metastasis. Therefore, understanding these interactions within the TME is crucial for the development of innovative cancer treatments. Extracellular vesicles (EVs) serve as carriers of various materials that include microRNAs, proteins, and lipids that play a vital role in the communication between tumour cells and non-tumour cells. EVs are actively involved in the metabolic reprogramming process. This review summarized recent findings regarding the involvement of EVs in the metabolic reprogramming of various cells in the TME of gastrointestinal cancers. Additionally, we highlight identified microRNAs involved in the reprogramming process in this group of cancers and explained the abnormal tumour metabolism targeted by exosomal cargos as well as the novel potential therapeutic approaches.

在肿瘤微环境(TME)中,促肿瘤和抗肿瘤网络之间存在复杂的相互作用。在整个肿瘤发生过程中,恶性细胞和TME的各种细胞之间的通讯有助于代谢重编程。肿瘤代谢途径的失调在TME中提供了进化优势,并增强了肿瘤的进展、侵袭性和转移。因此,了解TME中的这些相互作用对于开发创新的癌症治疗至关重要。细胞外小泡(EV)是各种材料的载体,包括在肿瘤细胞和非肿瘤细胞之间的通讯中发挥重要作用的微小RNA、蛋白质和脂质。EVs积极参与代谢重编程过程。这篇综述总结了EVs参与胃肠道癌症TME中各种细胞代谢重编程的最新发现。此外,我们强调了在这组癌症中参与重编程过程的已鉴定的微小RNA,并解释了外泌体货物靶向的异常肿瘤代谢以及新的潜在治疗方法。
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引用次数: 0
Extracellular vesicles as a novel mediator of interkingdom communication 细胞外小泡作为一种新的王国间通讯媒介。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.08.005
Jumin Huang , Xuanrun Wang , Ziming Wang , Liyan Deng , Yuwei Wang , Yuping Tang , Lianxiang Luo , Elaine Lai-Han Leung

Extracellular vesicles (EVs) are nanosized lipid bilayer-delimited particles secreted from almost all types of cells including bacteria, mammals and plants, and are presumed to be mediators of intercellular communication. Bacterial extracellular vesicles (BEVs) are nanoparticles with diverse diameters, ranging from 20 to 400 nm. BEVs are composed of soluble microbial metabolites, including nucleic acid, proteins, lipoglycans, and short-chain fatty acids (SCFAs). In addition, EVs may contain quorum sensing peptides that are endowed with the ability to protect bacteria against bacteriophages, form and maintain bacterial communities, and modulate the host immune system. BEVs are potentially promising therapeutic modalities for use in vaccine development, cancer immunotherapy regimens, and drug delivery cargos. Plant-derived EVs (PEVs), such as EVs derived from herbal medicines, can be absorbed by the gut microbiota and influence the composition and homeostasis of gut microbiota. This review highlights the roles of BEVs and PEVs in bacterial and plant physiology and discusses crosstalk among gut bacteria, host metabolism and herbal medicine. In summary, EVs represent crucial communication messengers in the gut microbiota, with potential therapeutic value in the delivery of herbal medicines.

细胞外小泡(EVs)是由包括细菌、哺乳动物和植物在内的几乎所有类型的细胞分泌的纳米大小的脂质双层界定的颗粒,被认为是细胞间通讯的介质。细菌细胞外小泡(BEV)是具有不同直径的纳米颗粒,直径从20到400nm不等。BEV由可溶性微生物代谢产物组成,包括核酸、蛋白质、脂聚糖和短链脂肪酸(SCFA)。此外,EVs可能含有群体感应肽,这些肽被赋予保护细菌免受噬菌体侵害、形成和维持细菌群落以及调节宿主免疫系统的能力。BEV是用于疫苗开发、癌症免疫疗法和药物输送货物的潜在有前途的治疗模式。植物衍生的EV(PEV),如草药衍生的EV,可以被肠道微生物群吸收,并影响肠道微生物群的组成和稳态。这篇综述强调了纯电动汽车和PEV在细菌和植物生理学中的作用,并讨论了肠道细菌、宿主代谢和草药之间的相互作用。总之,EVs是肠道微生物群中至关重要的通讯信使,在草药递送方面具有潜在的治疗价值。
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引用次数: 4
Role of lipid signalling in extracellular vesicles-mediated cell-to-cell communication 脂质信号传导在细胞外小泡介导的细胞间通讯中的作用。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.08.006
Jordan Fyfe , Ilaria Casari , Marcello Manfredi , Marco Falasca

Lipid signalling plays a crucial role in extracellular vesicle (EV)-mediated cell-to-cell communication. Extracellular vesicles are small membrane-bound structures released by various cell types into the extracellular environment. They include exosomes, microvesicles, and apoptotic bodies. These vesicles contain a variety of bioactive molecules, including proteins, nucleic acids (such as miRNAs and mRNAs), and lipids. Lipids are important components of EVs and are involved in various aspects of their biogenesis, cargo sorting, and functional effects on target cells. In this review, we will discuss how lipid signalling is involved in EV-mediated cell-to-cell communication. In summary, lipid signalling is intricately involved in extracellular vesicle-mediated cell-to-cell communication. The lipid composition of EVs influences their biogenesis, cargo sorting, interactions with target cells, and functional effects on recipient cells. Understanding the role of lipids in EV-mediated communication is essential for deciphering the mechanisms underlying intercellular signalling and developing potential therapeutic strategies based on EVs.

脂质信号传导在细胞外小泡(EV)介导的细胞间通讯中起着至关重要的作用。细胞外小泡是由各种细胞类型释放到细胞外环境中的小型膜结合结构。它们包括外泌体、微泡和凋亡小体。这些囊泡含有多种生物活性分子,包括蛋白质、核酸(如miRNA和mRNA)和脂质。脂质是EVs的重要组成部分,参与其生物发生、货物分拣和对靶细胞的功能影响的各个方面。在这篇综述中,我们将讨论脂质信号传导如何参与EV介导的细胞间通信。总之,脂质信号传导与细胞外小泡介导的细胞间通讯密切相关。EVs的脂质组成影响其生物发生、货物分拣、与靶细胞的相互作用以及对受体细胞的功能影响。了解脂质在EV介导的通讯中的作用对于破译细胞间信号传导的机制和开发基于EV的潜在治疗策略至关重要。
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引用次数: 1
Lipid metabolism in regulation of B cell development and autoimmunity 脂质代谢在调节B细胞发育和自身免疫中的作用。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.06.008
Xing Ji , Liang Wu , Tony Marion , Yubin Luo

B cells play an important role in adaptive immunity and participate in the process of humoral immunity mainly by secreting antibodies. The entire development and differentiation process of B cells occurs in multiple microenvironments and is regulated by a variety of environmental factors and immune signals. Differentiation biases or disfunction of B cells participate in the process of many autoimmune diseases. Emerging studies report the impact of altered metabolism in B cell biology, including lipid metabolism. Here, we discuss how extracellular lipid environment and metabolites, membrane lipid-related components, and lipid synthesis and catabolism programs coordinate B cell biology and describe the crosstalk of lipid metabolic programs with signal transduction pathways and transcription factors. We conclude with a summary of therapeutic targets for B cell lipid metabolism and signaling in autoimmune diseases and discuss important future directions.

B细胞在适应性免疫中起着重要作用,主要通过分泌抗体参与体液免疫过程。B细胞的整个发育和分化过程发生在多种微环境中,并受到各种环境因素和免疫信号的调节。B细胞的分化偏差或功能紊乱参与了许多自身免疫性疾病的过程。新兴的研究报告了B细胞生物学中代谢改变的影响,包括脂质代谢。在这里,我们讨论了细胞外脂质环境和代谢产物、膜脂质相关成分以及脂质合成和分解代谢程序如何协调B细胞生物学,并描述了脂质代谢程序与信号转导途径和转录因子的相互作用。最后,我们总结了自身免疫性疾病中B细胞脂质代谢和信号传导的治疗靶点,并讨论了未来的重要方向。
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引用次数: 0
The role of Extracellular Vesicles in glycolytic and lipid metabolic reprogramming of cancer cells: Consequences for drug resistance 细胞外囊泡在癌症细胞糖酵解和脂质代谢重编程中的作用:耐药性的后果。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.05.001
Bárbara Polónia , Cristina P.R. Xavier , Joanna Kopecka , Chiara Riganti , M. Helena Vasconcelos

In order to adapt to a higher proliferative rate and an increased demand for energy sources, cancer cells rewire their metabolic pathways, a process currently recognized as a hallmark of cancer. Even though the metabolism of glucose is perhaps the most discussed metabolic shift in cancer, lipid metabolic alterations have been recently recognized as relevant players in the growth and proliferation of cancer cells. Importantly, some of these metabolic alterations are reported to induce a drug resistant phenotype in cancer cells. The acquisition of drug resistance traits severely hinders cancer treatment, being currently considered one of the major challenges of the oncological field. Evidence suggests that Extracellular Vesicles (EVs), which play a crucial role in intercellular communication, may act as facilitators of tumour progression, survival and drug resistance by modulating several aspects involved in the metabolism of cancer cells. This review aims to gather and discuss relevant data regarding metabolic reprograming in cancer, particularly involving the glycolytic and lipid alterations, focusing on its influence on drug resistance and highlighting the relevance of EVs as intercellular mediators of this process.

为了适应更高的增殖率和对能源需求的增加,癌症细胞重新连接其代谢途径,这一过程目前被认为是癌症的标志。尽管葡萄糖代谢可能是癌症中讨论最多的代谢变化,但脂质代谢变化最近被认为是癌症细胞生长和增殖的相关因素。重要的是,据报道,这些代谢改变中的一些在癌症细胞中诱导耐药表型。耐药性特征的获得严重阻碍了癌症的治疗,目前被认为是肿瘤学领域的主要挑战之一。有证据表明,在细胞间通讯中发挥关键作用的细胞外小泡(EVs)可能通过调节癌症细胞代谢的几个方面,促进肿瘤进展、存活和耐药性。本综述旨在收集和讨论癌症代谢再编程的相关数据,特别是涉及糖酵解和脂质改变的数据,重点关注其对耐药性的影响,并强调EVs作为这一过程的细胞间介质的相关性。
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引用次数: 3
Role of exosomes in transferring chemoresistance through modulation of cancer glycolytic cell metabolism 外泌体在通过调节癌症糖酵解细胞代谢转移化疗耐药性中的作用。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.07.004
Mahrou Vahabi , Annalisa Comandatore , Marika A. Franczak , Ryszard T. Smolenski , Godefridus J. Peters , Luca Morelli , Elisa Giovannetti

Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.

化疗耐药性是癌症治疗的主要障碍,导致选择有限,患者存活率下降。最近的研究揭示了一种新的化学耐药性获取机制:通过外泌体(各种细胞分泌的小泡)传递信息。外泌体通过携带蛋白质、核酸和代谢产物,影响癌症细胞的行为和对治疗的反应,在细胞间通讯中发挥着至关重要的作用。抗药性的一个关键机制是癌症代谢重编程,它涉及细胞代谢途径的改变,以支持抗药性癌症细胞的生存和增殖。这种代谢重编程通常包括增加糖酵解,为癌症细胞提供必要的能量和构建块,以逃避化疗的影响。值得注意的是,外泌体已被发现运输糖酵解酶,如蛋白质组学分析中所确定的,导致代谢途径的重新编程,促进葡萄糖代谢的改变和乳酸产量的增加。因此,它们深刻影响肿瘤微环境,促进肿瘤进展、生存、免疫逃避和耐药性。了解这种外泌体介导的细胞间通讯的复杂性可能会开辟新的治疗途径,并促进生物标志物的开发,以管理具有侵袭性糖酵解特征的癌症。此外,鉴于代谢异常的复杂性,将未来的外泌体靶向治疗与化疗、免疫疗法和靶向治疗等现有治疗相结合,有望实现协同效应,克服耐药性,改善癌症治疗结果。
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引用次数: 0
Exosomes as a modulator of immune resistance in human cancers 外泌体作为人类癌症免疫抵抗的调节剂。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.07.007
Lanzhou Li , Chunyue Wang , Qiucheng Li , Yue Guan , Xin Zhang , Fange Kong , Zixin Feng , Yuanjun Lu , Di Wang , Ning Wang

In the tumor microenvironment (TME), exosomes secreted by cells form interactive networks between the tumor cells and immune cells, thereby regulating immune signaling cascades in the TME. As key messengers of cell-to-cell communication in the TME, exosomes not only take charge of tumor cell antigen presentation to the immune cells, but also regulate the activities of immune cells, inhibit immune function, and, especially, promote immune resistance, all of which affects the therapeutic outcomes of tumors. Exosomes, which are small-sized vesicles, possess some remarkable advantages, including strong biological activity, a lack of immunogenicity and toxicity, and a strong targeting ability. Based on these characteristics, research on exosomes as biomarkers or carriers of tumor therapeutic drugs has become a research hotspot in related fields. This review describes the role of exosomes in cell communications in the TME, summarizes the effectiveness of exosome-based immunotherapy in overcoming immune resistance in cancer treatment, and systematically summarizes and discusses the characteristics of exosomes from different cell sources. Furthermore, the prospects and challenges of exosome-related therapies are discussed.

在肿瘤微环境(TME)中,细胞分泌的外泌体在肿瘤细胞和免疫细胞之间形成相互作用的网络,从而调节TME中的免疫信号级联。外泌体作为TME中细胞间通讯的关键信使,不仅负责肿瘤细胞抗原向免疫细胞的呈递,还调节免疫细胞的活性,抑制免疫功能,尤其是促进免疫抵抗,所有这些都会影响肿瘤的治疗结果。外泌体是一种小型囊泡,具有生物活性强、缺乏免疫原性和毒性、靶向能力强等显著优点。基于这些特点,外泌体作为肿瘤治疗药物的生物标志物或载体的研究已成为相关领域的研究热点。这篇综述描述了外泌体在TME中细胞通讯中的作用,总结了基于外泌体的免疫疗法在癌症治疗中克服免疫抵抗的有效性,并系统总结和讨论了来自不同细胞来源的外泌体特征。此外,还讨论了外泌体相关疗法的前景和挑战。
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引用次数: 0
Liquid biopsy analysis of lipometabolic exosomes in pancreatic cancer 癌症脂肪代谢外泌体的液体活检分析。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.07.006
Wei Guo , Peiyao Ying , Ruiyang Ma , Zuoqian Jing , Gang Ma , Jin Long , Guichen Li , Zhe Liu

Pancreatic cancer is characterized by its high malignancy, insidious onset and poor prognosis. Most patients with pancreatic cancer are usually diagnosed at advanced stage or with the distant metastasis due to the lack of an effective early screening method. Liquid biopsy technology is promising in studying the occurrence, progression, and early metastasis of pancreatic cancer. In particular, exosomes are pivotal biomarkers in lipid metabolism and liquid biopsy of blood exosomes is valuable for the evaluation of pancreatic cancer. Lipid metabolism is crucial for the formation and activity of exosomes in the extracellular environment. Exosomes and lipids have a complex relationship of mutual influence. Furthermore, spatial metabolomics can quantify the levels and spatial locations of individual metabolites in cancer tissue, cancer stroma, and para-cancerous tissue in pancreatic cancer. However, the relationship among exosomes, lipid metabolism, and pancreatic cancer is also worth considering. This study mainly updates the research progress of metabolomics in pancreatic cancer, their relationship with exosomes, an important part of liquid biopsy, and their lipometabolic roles in pancreatic cancer. We also discuss the mechanisms by which possible metabolites, especially lipid metabolites through exosome transport and other processes, contribute to the recurrence and metastasis of pancreatic cancer.

癌症具有恶性程度高、发病隐匿、预后差等特点。由于缺乏有效的早期筛查方法,大多数癌症患者通常被诊断为晚期或远处转移。液体活检技术在研究癌症的发生、发展和早期转移方面具有很好的前景。特别是,外泌体是脂质代谢中的关键生物标志物,血液外泌体的液体活检对评估癌症有价值。脂质代谢对于外泌体在细胞外环境中的形成和活性至关重要。外泌体和脂质具有相互影响的复杂关系。此外,空间代谢组学可以量化癌症组织、癌症间质和癌症癌旁组织中个体代谢产物的水平和空间位置。然而,外泌体、脂质代谢和胰腺癌症之间的关系也值得考虑。本研究主要介绍癌症代谢组学的研究进展、代谢组学与液体活检重要组成部分外泌体的关系及其在癌症中的脂代谢作用。我们还讨论了可能的代谢产物,特别是通过外泌体转运和其他过程的脂质代谢产物,促进癌症复发和转移的机制。
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引用次数: 0
Extracellular vesicles in cancer: Shaping the intricate network of metabolic reprogramming and immune interactions in the tumor microenvironment 癌症的细胞外囊泡:在肿瘤微环境中形成代谢重编程和免疫相互作用的复杂网络。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.09.001
Elisa Giovannetti, Tian Li
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引用次数: 0
Proteomics analysis of circulating small extracellular vesicles: Focus on the contribution of EVs to tumor metabolism 循环细胞外小泡的蛋白质组学分析:关注EVs对肿瘤代谢的贡献。
IF 13 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.cytogfr.2023.08.003
Federica Anastasi , Asia Botto , Benoit Immordino , Elisa Giovannetti , Liam A. McDonnell

The term small extracellular vesicle (sEV) is a comprehensive term that includes any type of cell-derived, membrane-delimited particle that has a diameter < 200 nm, and which includes exosomes and smaller microvesicles. sEVs transfer bioactive molecules between cells and are crucial for cellular homeostasis and particularly during tumor development, where sEVs provide important contributions to the formation of the premetastic niche and to their altered metabolism. sEVs are thus legitimate targets for intervention and have also gained increasing interest as an easily accessible source of biomarkers because they can be rapidly isolated from serum/plasma and their molecular cargo provides information on their cell-of origin. To target sEVs that are specific for a given cell/disease it is essential to identify EV surface proteins that are characteristic of that cell/disease. Mass-spectrometry based proteomics is widely used for the identification and quantification of sEV proteins. The methods used for isolating the sEVs, preparing the sEV sample for proteomics analysis, and mass spectrometry analysis, can have a strong influence on the results and requires careful consideration. This review provides an overview of the approaches used for sEV proteomics and discusses the inherent compromises regarding EV purity versus depth of coverage. Additionally, it discusses the practical applications of the methods to unravel the involvement of sEVs in regulating the metabolism of pancreatic ductal adenocarcinoma (PDAC). The metabolic reprogramming in PDAC includes enhanced glycolysis, elevated glutamine metabolism, alterations in lipid metabolism, mitochondrial dysfunction and hypoxia, all of which are crucial in promoting tumor cell growth. A thorough understanding of these metabolic adaptations is imperative for the development of targeted therapies to exploit PDAC's vulnerabilities.

术语小细胞外小泡(sEV)是一个综合术语,包括任何类型的细胞衍生的、膜界定的直径为
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引用次数: 0
期刊
Cytokine & Growth Factor Reviews
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