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外泌体(extracellular vesicles,EVs)是各类细胞(尤其是肿瘤细胞)释放的一种能介导遗传物质传递的磷脂双层膜的囊泡样小体。外泌体中含有受体、蛋白质和核酸,具有携带肿瘤遗传物质,调节肿瘤微环境,促进肿瘤血管生成及介导肿瘤细胞转移等功能。目前研究发现外泌体与肺癌脑转移瘤关系密切。外泌体介导的肺癌脑转移主要包括调节脑部预转移巢微环境,破坏血脑屏障,调节瘤细胞病理特征等过程。外泌体与肺癌脑转移瘤关系的研究为肺癌脑转移瘤的发生发展、临床诊断和治疗研究提供了更多分子靶点。 相似文献
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肿瘤的化疗药物耐药是指肿瘤细胞对药物的敏感性降低,使药物的疗效下降甚至无效的现象,是肿瘤化疗失败的重要原因。外泌体是一类细胞外囊泡,由肿瘤微环境中的癌细胞和多种基质细胞分泌。外泌体可通过将它们的内含物(包括DNA、RNA、蛋白质和脂质等)转移到癌细胞中增加化疗药物抗性;同时外泌体的损耗也会逆转某些不利于肿瘤代谢的影响因素,并恢复对化疗药物的敏感性。非编码RNA(ncRNA)为不具备编码蛋白质功能的基因组转录产物,在基因转录、转录后及翻译水平发挥调控作用。研究较多的ncRNA包括微小RNA(microRNA)、长链非编码RNA(lncRNA)和环状RNA(circRNA)等。近年来的研究发现,外泌体非编码RNA在细胞间通信中起着关键作用,能够影响肿瘤的发生、发展、转移、侵袭、肿瘤微环境以及耐药性。对肿瘤耐药相关的外泌体ncRNA进行研究,已经揭示了外泌体ncRNA在耐药与肿瘤发展中的一些分子机制、靶点通路以及功能。本文对microRNA、lncRNA和circRNA等外泌体ncRNA在肿瘤耐药中的相关功能和作用机制展开综述,希望对研究肿瘤耐药的液体活检分子标志物,理解肿瘤耐药的新机制,肿... 相似文献
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《中华乳腺病杂志(电子版)》2021,(2)
乳腺癌是女性发病率最高的恶性肿瘤。早期乳腺癌患者中的30%能够检测到循环肿瘤细胞,这是导致约90%乳腺癌患者转移致死的主要原因。外泌体是一系列具有生物功能的小囊泡,携带多种活性成分,不同类型供体细胞来源的外泌体均可影响乳腺癌细胞和基质细胞,在肿瘤微环境中发挥不同的作用,调控乳腺癌的转移。笔者从外泌体影响肿瘤微环境、转移前生态位形成、循环肿瘤细胞在血液和靶器官中存活机制等方面,综述了外泌体在乳腺癌进展和转移中的作用。 相似文献
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外泌体是细胞间通信的多功能调节剂,通过携带各种信息在肿瘤患者的生理和病理状态下起作用。越来越多的研究已经确定了环状RNA(circRNA)在多种细胞中具有关键的调节作用,来自供体细胞的外泌体circRNA可以局部或远程调节受体细胞,以促进肿瘤的发展和传播,并在肿瘤微环境(TME)中发挥关键作用,从而显著增强肿瘤免疫、代谢、血管生成、耐药性、上皮-间充质转化(EMT)、侵袭和转移。本文主要综述了外泌体circRNA在TME中的潜在作用,强调了外泌体circRNA是肿瘤的生物标志物和潜在治疗靶点,为今后肿瘤的诊断和治疗提供帮助。 相似文献
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背景与目的:乳腺癌是全球女性发病率最高的恶性肿瘤,患者预后差。肿瘤源性外泌体会改变肿瘤微环境并参与调控肿瘤的发生、发展及转移,这将为肿瘤的诊断和治疗提供新的思路。DZNep能够靶向调控H3K27me3组蛋白甲基转移酶的降解,并特异性地诱导肿瘤细胞凋亡,从而抑制多种肿瘤细胞增殖和迁移。本研究旨在探索DZNep对乳腺癌源性外泌体的影响,并观察其通过调节细胞间连接从而改变乳腺癌细胞上皮-间充质转化(epithelial-mesenchymal transition,EMT)的作用。方法:应用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库和在线分析软件GEPIA2分析EZH2在乳腺癌中的表达,使用肿瘤免疫估计资源(Tumor Immunity Estimation Resources,TIMER)分析EZH2与肿瘤微环境中细胞因子及EMT相关蛋白表达的关系。采用DZNep干预乳腺癌MDA-MB-231细胞,采用差速超速离心法提取外泌体,采用蛋白质印迹法(Western blot)检测CD9、CD63和TSG101的表达情况并鉴定外泌体膜结合蛋白的表达,采用纳米... 相似文献
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肺癌发病率和死亡率位居世界癌症前列。超过80%的肺癌为非小细胞肺癌(non-small cell lung cancer,NSCLC),大多数患者在最初就诊时已出现局部进展或转移性疾病。外泌体是一种膜结合纳米囊泡,由活细胞释放,含有多种生物分子,如蛋白质、RNA、代谢物,甚至是药理化合物。外泌体广泛地分布于体液中,包括血浆、唾液、母乳、脑脊液等。越来越多的证据表明,外泌体在NSCLC的发生、微环境、治疗和耐药等方面发挥着重要作用。在这篇综述中,我们将对NSCLC来源的外泌体在肿瘤生长、转移、免疫应答和耐药等方面的作用进行综述。最后,我们将展望外泌体在非小细胞肺癌中的临床价值。 相似文献
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转移和耐药的发生是黑色素瘤逃脱靶向化疗药物毒性伤害的主要方式,也是导致临床靶向治疗失败和病情复发的最重要因素。外泌体是由细胞分泌的外囊泡,内含微小RNA(miRNA)、mRNA、小分子蛋白等多种生物活性物质,在肿瘤进展、诊断等方面发挥重要作用。外泌体miRNA通过协助黑色素瘤细胞穿过基底膜,诱导上皮间质转化(epithelial-mesenchymal transition,EMT),促进转移前微环境建立,参与黑色素瘤转移。同时在化疗药物治疗过程中,外泌体miRNA通过进入黑色素瘤细胞中重新激活MAPK/PI3K信号通路,进而导致耐药产生。因此,探究外泌体miRNA在黑色素瘤转移和耐药过程中的功能和机制作用对于提高和改善癌症患者的治愈率和预后状态具有重要意义。 相似文献
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Duc‐Hiep Bach Ji‐Young Hong Hyen Joo Park Sang Kook Lee 《International journal of cancer. Journal international du cancer》2017,141(2):220-230
Chemotherapy, one of the principal approaches for cancer patients, plays a crucial role in controlling tumor progression. Clinically, tumors reveal a satisfactory response following the first exposure to the chemotherapeutic drugs in treatment. However, most tumors sooner or later become resistant to even chemically unrelated anticancer agents after repeated treatment. The reduced drug accumulation in tumor cells is considered one of the significant mechanisms by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell membrane. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated, including drug efflux, which is mediated by extracellular vesicles (EVs). Exosomes, a subset of EVs with a size range of 40–150 nm and a lipid bilayer membrane, can be released by all cell types. They mediate specific cell‐to‐cell interactions and activate signaling pathways in cells they either fuse with or interact with, including cancer cells. Exosomal RNAs are heterogeneous in size but enriched in small RNAs, such as miRNAs. In the primary tumor microenvironment, cancer‐secreted exosomes and miRNAs can be internalized by other cell types. MiRNAs loaded in these exosomes might be transferred to recipient niche cells to exert genome‐wide regulation of gene expression. How exosomal miRNAs contribute to the development of drug resistance in the context of the tumor microenvironment has not been fully described. In this review, we will highlight recent studies regarding EV‐mediated microRNA delivery in formatting drug resistance. We also suggest the use of EVs as an advancing method in antiresistance treatment. 相似文献
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卵巢癌(ovarian cancer,OC)是女性恶性肿瘤死亡的主要原因。由于卵巢癌无症状发展,缺乏早期诊断标志物,大多数患者在晚期才被诊断出来。早期检测卵巢癌可显著提高总生存率,在过去的几十年里,微小RNA(miRNA)在癌症的发展中起着重要的作用,因此引起了极大的关注。miRNA可以在循环血液中稳定存在(如包裹在外泌体中),并可通过外泌体的分泌和转移在肿瘤细胞之间和肿瘤细胞微环境的沟通中发挥重要的作用。此外,外泌体miRNA在卵巢癌中的表达是失调的,可能反映肿瘤的恶性特征。因此评估外泌体来源的循环miRNA可能会为卵巢癌提供一类新的非侵袭性生物标志物。本综述概述了有关外泌体miRNA在卵巢癌发生发展过程中的作用以及循环血液外泌体miRNA作为卵巢癌早期诊断潜在生物标志物的现状。 相似文献
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外泌体是一类直径为30~100 nm的圆盘囊泡,其内包含许多组分,诸如复杂RNA和蛋白质等,主要参与细胞间的信号转导。肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是肿瘤微环境中普遍存在的巨噬细胞,通过对肿瘤生长、免疫逃逸、侵袭和转移、耐药性等多方面的作用影响肿瘤进程。外泌体在肿瘤相关巨噬细胞的招募、极化及抗肿瘤免疫调控等方面发挥着重要的调节功能。同时,TAMs以外泌体为媒介作用于肿瘤细胞,从而构成了外泌体、TAMs与肿瘤细胞之间相互作用的调控通路。综上所述,本文旨在阐明肿瘤细胞与TAMs之间,以外泌体为“桥梁”相互影响的潜在机制,以及靶向肿瘤细胞和TAMs来源的外泌体在恶性肿瘤治疗中的展望。 相似文献
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Nicolas Bovy Beno?t Blomme Pierre Frères Stella Dederen Olivier Nivelles Michelle Lion Oriane Carnet Joseph A. Martial Agnès No?l Marc Thiry Guy Jérusalem Claire Josse Vincent Bours Sébastien P. Tabruyn Ingrid Struman 《Oncotarget》2015,6(12):10253-10266
The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment. 相似文献
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Dan‐dan Yu Ying Wu Hong‐yu Shen Meng‐meng Lv Wei‐xian Chen Xiao‐hui Zhang Shan‐liang Zhong Jin‐hai Tang Jian‐hua Zhao 《Cancer science》2015,106(8):959-964
Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano‐sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life‐threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome‐delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti‐cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti‐cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system. 相似文献