Luize G Lima, Sunyoung Ham, Hyunku Shin, Edna P Z Chai, Erica S H Lek, Richard J Lobb, Alexandra F Müller, Suresh Mathivanan, Belinda Yeo, Yeonho Choi, Belinda S Parker, Andreas Möller
Metastatic spread of a cancer to secondary sites is a coordinated, non-random process. Cancer cell-secreted vesicles, especially exosomes, have recently been implicated in the guidance of metastatic dissemination, with specific surface composition determining some aspects of organ-specific localization. Nevertheless, whether the tumor microenvironment influences exosome biodistribution has yet to be investigated. Here, we show that microenvironmental cytokines, particularly CCL2, decorate cancer exosomes via binding to surface glycosaminoglycan side chains of proteoglycans, causing exosome accumulation in specific cell subsets and organs...
June 10, 2021: Nature Communications
Zheng Zhang, Hao Guo, Wenjia Yang, Jiuhong Li
Objective: Aberrantly expressed exosomal circular RNAs (circRNAs) have been reported in various human cancers. Nevertheless, it remains elusive in cutaneous squamous cell carcinoma (cSCC). Herein, based on RNA-seq, we systematically uncovered the expression and implication of exosomal circRNAs in cSCC. Methods: Plasma exosomes derived from cSCC and healthy subjects were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blot. Differentially expressed exosomal circular RNAs (circRNAs) were screened by RNA-seq analysis, which were validated by RT-qPCR...
2021: Frontiers in Medicine
Maedeh Arabpour, Amene Saghazadeh, Nima Rezaei
Mesenchymal stem cells (MSCs) are multipotent cells beneficial in regenerative medicine and tissue repair. The therapeutic potential of MSCs for inflammatory diseases and conditions is partly due to secreted exosomes. Exosomes are one group of extracellular vesicles with 50-150 nm in diameter. They can carry numerous molecules and introduce them to the recipient cells to produce various biological effects. Macrophages are classified into M1 and M2 subtypes based on their activation states. M1 macrophages release pro-inflammatory factors like tumor necrosis factoralfa (TNF-α), interleukin1alfa (IL-1α), interleukin1beta (IL-1β), interleukin6 (IL-6), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10), while M2 macrophages secrete anti-inflammatory mediators including interleukin10 (IL-10), transforming growth factor beta (TGF-β), C-C motif chemokine ligand 1 (CCL1), C-C motif chemokine ligand 17 (CCL17), C-C motif chemokine ligand 18 (CCL18), and C-C motif chemokine ligand 22 (CCL22)...
June 4, 2021: International Immunopharmacology
Yan Zhou, Lu-Lu Wen, Yan-Fei Li, Kai-Min Wu, Ran-Ran Duan, Yao-Bing Yao, Li-Jun Jing, Zhe Gong, Jun-Fang Teng, Yan-Jie Jia
Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear...
January 2022: Neural Regeneration Research
Shuqi He, Wu Zhang, Xian Li, Junjie Wang, Xufeng Chen, Yu Chen, Renfa Lai
Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity. Studies have shown that exosomal miRNAs from cancer cells play an important role in mediating the cellular environment. The objective was to investigate the effect of OSCC-derived exosomes microRNA-221 (miR-221) in OSCC. We used quantitative real-time PCR (qRT-PCR) and western blotting to determine PIK3R1 and miR-221 expressions in OSCC tissue or peripheral blood serum. Exosomes of OSCC cell line CAL27 were extracted and characterized...
December 2021: Bioengineered
Li Ba, Chunling Xue, Xuechun Li, Mingjia Zhang, Ying Yang, Qin Han, Zhao Sun, Robert Chunhua Zhao
As an important component of the dynamic tumor microenvironment, mesenchymal stem cells (MSCs) can interact with tumor cells to promote tumor growth. Treatment with tumor cell-derived exosomes can change the biological functions of MSCs. We want to study the mechanism by which exosomes derived from gastric cancer cells affect the biological functions of MSCs. After MSCs were treated with AGS cell-derived exosomes, circular RNAs differentially expressed in MSCs were verified using existing RNA microarray results combined with real-time quantitative polymerase chain reaction (qRT-PCR)...
June 7, 2021: Stem Cells and Development
Junfang Tu, Xun Luo, Haitao Liu, Jifeng Zhang, Mei He
Cancer cell spheroids have been shown to be more physiologically relevant to native tumor tissue than monolayer 2D culture cells. Due to enhanced intercellular communications among cells in spheroids, spheroid secreted exosomes which account for transcellular transportation should exceed those from 2D cell culture and may display a different expression pattern of miRNA or protein. To test this, we employed a widely used pancreatic cancer cell line, PANC-1, to create 3D spheroids and compared exosomes generated by both 2D cell culture and 3D PANC-1 spheroids...
July 2021: Biochemistry and Biophysics Reports
Chunxiao Miao, Wanli Zhang, Lixing Feng, Xiaofan Gu, Qiang Shen, Shanshan Lu, Meng Fan, Yiwei Li, Xianling Guo, Yushui Ma, Xuan Liu, Hui Wang, Xiongwen Zhang
Cancer cachexia is a kind of whole-body metabolic disorder syndrome accompanied by severe wasting of muscle tissue in which cancer exosomes may be involved. Analysis of clinical samples showed that the serum exosome concentrations were correlated with the development of cancer cachexia. Exosomes secreted by C26 cells could decrease the diameter of C2C12 myotubes in vitro and decrease mouse muscle strength and tibialis anterior (TA) muscle weight in vivo . GW4869, an inhibitor of exosome excretion, ameliorated muscle wasting in C26 tumor-bearing mice...
June 4, 2021: Molecular Therapy. Nucleic Acids
Jing Xun, Lingfang Du, Ruifang Gao, Long Shen, Dekun Wang, Lichun Kang, Chuan'ai Chen, Zhujun Zhang, Yuying Zhang, Shijing Yue, Shuxin Feng, Rong Xiang, Xue Mi, Xiaoyue Tan
Rationale: Differential activation of macrophages correlates closely with tumor progression, and the epigenetic factor lysine demethylase 6B (KDM6B, previously named JMJD3) mediates the regulation of macrophage polarization through an unknown mechanism. Methods: We developed a suspension coculture system comprising breast cancer cells and macrophages and used RT-qPCR and western blotting to measure KDM6B expression. Bioinformatics and luciferase reporter assays were used to identify candidate microRNAs of cancer cells responsible for the downregulation of KDM6B...
2021: Theranostics
Yu Zhou, Fan Chen, Xiaodong Xie, Huifang Nie, Shu Lian, Chunlian Zhong, Chengbin Fu, Weiyu Shen, Bifei Li, Yongqing Ye, Yusheng Lu, Lee Jia
Although tumor-derived exosomes play an important role in the process of metastasis, differences in exosomes secreted by the same cells at different stages or conditions have not been noticed by most of the relevant researchers. Here we developed a lung cancer model in nude mice, and the phenotype and inclusions of exosomes secreted by early and advanced tumors were analysed. The size distribution and surface topography of these two exosomes were not significantly different, but the expression of CD63 in early tumor exosome (E-exosome) was significantly lower than that in advanced tumor exosome (A-exosome)...
2021: Journal of Cancer
Alberto J L Macario, Everly Conway de Macario
The chaperonins CCT and Hsp60 are molecular chaperones, members of the chaperone system (CS). Chaperones are cytoprotective but if abnormal in quantity or quality they may cause diseases, the chaperonopathies. Here, recent advances in the understanding of CCT and Hsp60 in cancerology are briefly discussed, focusing on breast and brain cancers. CCT subunits, particularly CCT2, were increased in breast cancer cells and this correlated with tumor progression. Experimental induction of CCT2 increase was accompanied by an increase of CCT3, 4, and 5, providing another evidence for the interconnection between the members of the CS and the difficulties expected while manipulating one member with therapeutic purposes...
June 1, 2021: Seminars in Cancer Biology
Yi Yuan, Zeyu Wang, Mengqi Chen, Yang Jing, Wei Shu, Zhuoying Xie, Zhiyang Li, Juanyong Xu, Feng He, Pengfei Jiao, Jiaqing Wang, Jiamin Xu, Yan Xia, Siyu Liu, Hongming Du, Hongwei Li, Lu Dai, Youjin Dai, Yaqin Zhang
Tumour-associated macrophages (TAMs) are thought to contribute to oral squamous cell carcinoma (OSCC) initiation and progression. However, the underlying mechanism through which TAMs foster OSCC progression is still unclear. This study intended to determine whether there are exclusively exosomal miRNAs-derived macrophages that are functionally necessary for OSCC progression. The phenotype of TAM recruitment in OSCC tissue samples was assessed, subsequently identifying the influence of M2 macrophages and exosomes derived from M2 macrophages on OSCC proliferation and tumorigenesis in vitro and in vivo...
May 1, 2021: Journal of Biomedical Nanotechnology
Pei-Pei Hou, Hang-Zi Chen
Extracellular vesicles (EVs) have gained significant attention in recent decades as major mediators of intercellular communication that are involved in various essential physiological and pathological processes. They are secreted by almost all cell types and carry bioactive materials, such as proteins, lipids and nucleic acids, that can be transmitted from host cells to recipient cells, thereby eliciting phenotypic and functional alterations in the recipient cells. Recent evidence shows that EVs play essential roles in remodeling the tumor immune microenvironment (TIME)...
May 31, 2021: Cancer Letters
Xin Yang, Yan Chen, You Zhou, Chen Wu, Qing Li, Jun Wu, Wen Wei Hu, Wei Qing Zhao, Wei Wei, Chang Ping Wu, Jing Ting Jiang, Mei Ji
Lung cancer is the leading cause of cancer-related death worldwide. Glypican-5 (GPC5) is a member of heparan sulfate proteoglycans, and its biological importance in initiation and progression of lung cancer remains controversial. In the present study, we revealed that GPC5 transcriptionally enhanced the expression of CTDSP1 (miR-26b host gene) via AhR-ARNT pathway, and such up-regulation of CTDSP1 intracellularly contributed to the inhibited proliferation of lung cancer cells. Moreover, exosomes derived from GPC5-overexpressing human lung cancer cells (GPC5-OE-derived exosomes) had an extracellular repressive effect on human lymphatic endothelial cells (hLECs), leading to decreased tube formation and migration...
June 2, 2021: Oncogene
Reza Hosseini, Leila Asef-Kabiri, Hassan Yousefi, Hamzeh Sarvnaz, Majid Salehi, Mohammad Esmaeil Akbari, Nahid Eskandari
Tumor-derived exosomes (TDEs) have been shown to impede anti-tumor immune responses via their immunosuppressive cargo. Since dendritic cells (DCs) are the key mediators of priming and maintenance of T cell-mediated responses; thus it is logical that the exosomes released by tumor cells can exert a dominant influence on DCs biology. This paper intends to provide a mechanistic insight into the TDEs-mediated DCs abnormalities in the tumor context. More importantly, we discuss extensively how tumor exosomes induce subversion of DCs differentiation, maturation and function in separate sections...
June 2, 2021: Molecular Cancer
Beiyou Lin, Wenchao Xie, Chunmei Zeng, Xiaodan Wu, Ang Chen, Hao Li, Rina Jiang, Ping Li
Dendritic cell-derived exosomes have been proven to be efficient adjuvant options for anti-tumor vaccines in cancer immunotherapy. However, their potency in atherosclerosis remains unclear. Here we summarize the association of microRNA-203-3p (miR-203-3p) with dendritic cell-derived exosomes and atherosclerosis. Firstly, dendritic cell-derived exosomes and bone marrow-derived macrophages were isolated, after which expression of miR-203-3p and cathepsin S was determined. After the establishment of atherosclerosis mouse models, gain- and loss-of-function experiments were conducted for the analysis of effects of miR-203-3p and cathepsin S on foam-cell formation, lipid accumulation, collagen deposition and serum total cholesterol...
June 2, 2021: Aging
Fengqiang Yu, Mingqiang Liang, Yu Huang, Weidong Wu, Bin Zheng, Chun Chen
BACKGROUND: Exosomes have emerged as critical mediators of intercellular communication. Hypoxia is widely recognized as a key regulator of tumor aggressiveness, and significantly affects exosome release by tumor cells. However, the effects of exosomes derived from hypoxic lung adenocarcinoma (LUAD) cells are poorly understood. METHODS: Samples of miRNA isolated from hypoxic LUAD cell-derived exosomes (HExo) and normoxic LUAD cell-derived exosomes (NExo) were sequenced to identify miRNAs that might mediate tumor progression...
June 1, 2021: Journal of Experimental & Clinical Cancer Research: CR
Rabab N Hamzah, Karrer M Alghazali, Alexandru S Biris, Robert J Griffin
Exosomes are small vesicles with an average diameter of 100 nm that are produced by many, if not all, cell types. Exosome cargo includes lipids, proteins, and nucleic acids arranged specifically in the endosomes of donor cells. Exosomes can transfer the donor cell components to target cells and can affect cell signaling, proliferation, and differentiation. Important new information about exosomes' remote communication with other cells is rapidly being accumulated. Recent data indicates that the results of this communication depend on the donor cell type and the environment of the host cell...
May 19, 2021: International Journal of Molecular Sciences
Csongor György Lengyel, Sadaqat Hussain, Dario Trapani, Khalid El Bairi, Sara Cecilia Altuna, Andreas Seeber, Andrew Odhiambo, Baker Shalal Habeeb, Fahmi Seid
(1) Background: Liquid biopsy (LB) is a novel diagnostic method with the potential of revolutionizing the prevention, diagnosis, and treatment of several solid tumors. The present paper aims to summarize the current knowledge and explore future possibilities of LB in the management of metastatic gastric cancer. (2) Methods: This narrative review examined the most recent literature on the use of LB-based techniques in metastatic gastric cancer and the current LB-related clinical trial landscape. (3) Results: In gastric cancer, the detection of circulating cancer cells (CTCs) has been recognized to have a prognostic role in all the disease stages...
May 13, 2021: Journal of Clinical Medicine
Ombretta Repetto, Federica Lovisa, Caterina Elia, Daniel Enderle, Filippo Romanato, Salvatore Buffardi, Alessandra Sala, Marta Pillon, Agostino Steffan, Roberta Burnelli, Lara Mussolin, Maurizio Mascarin, Valli De Re
Exosomes and other small extracellular vesicles (EVs) are potential sources of cancer biomarkers. Plasma-derived EVs have not yet been studied in pediatric Hodgkin lymphoma (HL), for which predictive biomarkers of relapse are greatly needed. In this two-part proteomic study, we used two-dimensional difference gel electrophoresis (2D-DIGE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze EV proteins of plasma collected at diagnosis from children with nodular sclerosis HL, relapsed or not...
May 21, 2021: Diagnostics
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