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https://www.readbyqxmd.com/read/29335551/tumor-derived-exosomal-mir-1247-3p-induces-cancer-associated-fibroblast-activation-to-foster-lung-metastasis-of-liver-cancer
#1
Tian Fang, Hongwei Lv, Guishuai Lv, Ting Li, Changzheng Wang, Qin Han, Lexing Yu, Bo Su, Linna Guo, Shanna Huang, Dan Cao, Liang Tang, Shanhua Tang, Mengchao Wu, Wen Yang, Hongyang Wang
The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin-NF-κB signaling in fibroblasts...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29320704/extracellular-vesicles-provide-a-means-for-tissue-crosstalk-during-exercise
#2
Martin Whitham, Benjamin L Parker, Martin Friedrichsen, Janne R Hingst, Marit Hjorth, William E Hughes, Casey L Egan, Lena Cron, Kevin I Watt, Rhiannon P Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M Suter, Paul Gregorevic, Bente Kiens, Erik A Richter, David E James, Jørgen F P Wojtaszewski, Mark A Febbraio
Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative proteomic techniques to characterize the exercise-induced secretion of EV-contained proteins. Following a 1-hr bout of cycling exercise in healthy humans, we observed an increase in the circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles...
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29296848/enhanced-liver-gene-transfer-and-evasion-of-preexisting-humoral-immunity-with-exosome-enveloped-aav-vectors
#3
Amine Meliani, Florence Boisgerault, Zachary Fitzpatrick, Solenne Marmier, Christian Leborgne, Fanny Collaud, Marcelo Simon Sola, Severine Charles, Giuseppe Ronzitti, Alban Vignaud, Laetitia van Wittenberghe, Beatrice Marolleau, Fabienne Jouen, Sisareuth Tan, Olivier Boyer, Olivier Christophe, Alain R Brisson, Casey A Maguire, Federico Mingozzi
Results from clinical trials of liver gene transfer for hemophilia demonstrate the potential of the adeno-associated virus (AAV) vector platform. However, to achieve therapeutic transgene expression, in some cases high vector doses are required, which are associated with a higher risk of triggering anti-capsid cytotoxic T-cell responses. Additionally, anti-AAV preexisting immunity can prevent liver transduction even at low neutralizing antibody (NAb) titers. Here, we describe the use of exosome-associated AAV (exo-AAV) vectors as a robust liver gene delivery system that allows the therapeutic vector dose to be decreased while protecting from preexisting humoral immunity to the capsid...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29286922/lncrna-heih-in-serum-and-exosomes-as-a-potential-biomarker-in-the-hcv-related-hepatocellular-carcinoma
#4
Chun Zhang, Xi Yang, Quan Qi, Yuhai Gao, Qiang Wei, Shuwen Han
BACKGROUND: Chronic hepatitis C (CHC) is a contagious liver disease that results from infection with the hepatitis C virus (HCV). The most serious consequence of CHC is HCV-related hepatocellular carcinoma (HCC). OBJECTIVE: To illustrate the clinical significance of lncRNA HEIH expression in serum and exosomes in the development of HCV-related HCC. METHODS: Thirty-five CHC, twenty-two HCV-induced cirrhosis and ten HCV-related HCC patients in Huzhou Central Hospital from January 2016 to September 2016 were recruited in the present study...
December 22, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29283887/exosomal-micrornas-derived-from-colorectal-cancer-associated-fibroblasts-role-in-driving-cancer-progression
#5
Rahul Bhome, Rebecca W Goh, Marc D Bullock, Nir Pillar, Stephen M Thirdborough, Massimiliano Mellone, Reza Mirnezami, Dieter Galea, Kirill Veselkov, Quan Gu, Timothy J Underwood, John N Primrose, Olivier De Wever, Noam Shomron, A Emre Sayan, Alex H Mirnezami
Colorectal cancer is a global disease with increasing incidence. Mortality is largely attributed to metastatic spread and therefore, a mechanistic dissection of the signals which influence tumor progression is needed. Cancer stroma plays a critical role in tumor proliferation, invasion and chemoresistance. Here, we sought to identify and characterize exosomal microRNAs as mediators of stromal-tumor signaling. In vitro, we demonstrated that fibroblast exosomes are transferred to colorectal cancer cells, with a resultant increase in cellular microRNA levels, impacting proliferation and chemoresistance...
December 28, 2017: Aging
https://www.readbyqxmd.com/read/29259715/clinical-trials-using-mesenchymal-stem-cells-in-liver-diseases-and-inflammatory-bowel-diseases
#6
REVIEW
Atsunori Tsuchiya, Yuichi Kojima, Shunzo Ikarashi, Satoshi Seino, Yusuke Watanabe, Yuzo Kawata, Shuji Terai
Mesenchymal stem cell (MSC) therapies have been used in clinical trials in various fields. These cells are easily expanded, show low immunogenicity, can be acquired from medical waste, and have multiple functions, suggesting their potential applications in a variety of diseases, including liver disease and inflammatory bowel disease. MSCs help prepare the microenvironment, in response to inflammatory cytokines, by producing immunoregulatory factors that modulate the progression of inflammation by affecting dendritic cells, B cells, T cells, and macrophages...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29240249/exosomal-mir-6803-5p-as-potential-diagnostic-and-prognostic-marker-in-colorectal-cancer
#7
Shushan Yan, Ye Jiang, Caihong Liang, Chengwen Jin, Quanhong Duan, Donghua Xu, Lu Yang, Xiaoyu Zhang, Bin Ren, Peng Jin
Accumulating data have suggested exosome-delivered microRNAs (miRNAs) play critical role in carcinogenesis and cancer progression. However, little is known about the influence of exosomal miR-6803-5p on the development and prognosis of colorectal cancer (CRC). Levels of serum exosomal miR-6803-5p were determined by microarray analysis and verified by quantitative real-time PCR (qRT-PCR). Outcomes of overall survival (OS) and disease-free survival (DFS) of CRC patients were estimated by Kaplan-Meier analysis...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29223394/islet-%C3%AE-cell-an-endocrine-cell-secreting-mirnas
#8
Aisen Zhang, Dameng Li, Yucheng Liu, Jing Li, Yujing Zhang, Chen-Yu Zhang
The pancreas is an important endocrine organ. Pancreatic beta (β) cells secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. MicroRNAs (miRNAs), small (20-25 nt) non-coding RNA molecules, function in target gene silencing through post-transcriptional patterns, and multiple miRNAs regulate insulin secretion, insulin signaling pathways in pancreatic β cells and islet activity. In recent years, it has been found that many types of cells can secrete regulatory miRNA, but whether islet cells can secrete miRNA has not been clarified yet...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29145157/bmscs-derived-mir-223-containing-exosomes-contribute-to-liver-protection-in-experimental-autoimmune-hepatitis
#9
Lu Chen, Feng-Bin Lu, Da-Zhi Chen, Jin-Lu Wu, En-de Hu, Lan-Man Xu, Ming-Hua Zheng, Hui Li, Yu Huang, Xiao-Ya Jin, Yue-Wen Gong, Zhuo Lin, Xiao-Dong Wang, Yong-Ping Chen
Autoimmune hepatitis is a chronic inflammatory disease in the liver with potential to the development of liver fibrosis. Recent evidences suggest that bone marrow derived mesenchymal stem cells (BMSCs) may exert its therapeutic activity through exosomes. Moreover, miR-223 is highly expressed in BMSCs and plays an important role in autoimmune diseases. Therefore, in this study, hepatoprotective role of BMSCs and miR-223 was investigated in both mice and hepatocytes. Liver antigen S100 was used to establish autoimmune hepatitis model in mice while LPS and ATP were used to establish cell injury model in hepatocyte...
November 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29138862/liver-kinase%C3%A2-b1-restoration-promotes-exosome-secretion-and-motility-of-lung-cancer-cells
#10
Cheng Zhang, Xiang Xiao, Minyi Chen, Hitham Aldharee, Yanfang Chen, Weiwen Long
Liver kinase B1 (LKB1) regulates a variety of cellular functions, including cell polarity, energy metabolism and cell growth, by targeting multiple signaling pathways such as AMPK/mTOR and p53. LKB1 functions as a tumor suppressor in sporadic cancers including lung cancer. Extracellular vesicles such as exosomes secreted by cancer cells modulate the tumor microenvironment and progression by targeting both tumor cells (autocrine actions) and other types of cells associated with tumors (paracrine actions). While the roles of LKB1 in cellular signaling in general is well-studied, its specific role in exosome-mediated signaling remains to be explored...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29137633/bi-directional-exosome-driven-intercommunication-between-the-hepatic-niche-and-cancer-cells
#11
Nikolina Dioufa, Amanda M Clark, Bo Ma, Colin H Beckwitt, Alan Wells
BACKGROUND: Our understanding of the multiple roles exosomes play during tumor progression is still very poor and the contribution of the normal tissue derived exosomes in distant seeding and tumor outgrowth has also not been widely appreciated. METHODS: Using our all-human liver microphysiological system (MPS) platform as a model to closely recapitulate the early metastatic events, we isolated exosomes from both tumor cells and liver microenvironment. RESULTS: We observed that while priming of the hepatic niche (HepN) with MDA-231 breast cancer derived exosomes facilitated seeding of the cancer cells in the liver, subsequent tumor outgrowth was diminished; this was consistent with increased entry into dormancy...
November 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29122679/extracellular-vesicles-novel-mediator-for-cell-to-cell-communications-in-liver-pathogenesis
#12
REVIEW
Pradip B Devhare, Ratna B Ray
Extracellular vesicles (EVs) are membrane derived nanometer-sized vesicles. EVs are released by normal, diseased, and transformed cells in vitro and in vivo, and carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. Transferring biological information via EVs to neighboring cells and inter-cellular communication not only maintain physiological functions, but also involve in the pathogenesis of several diseases, including cancer. The aim of this review is to discuss the emerging role of EVs in viral hepatitis, non-alcoholic or alcoholic liver disease and liver cancers...
November 10, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29108252/circulating-exosomal-microrna-203-is-associated-with-metastasis-possibly-via-inducing-tumor-associated-macrophages-in-colorectal-cancer
#13
Yuki Takano, Takaaki Masuda, Hisae Iinuma, Rui Yamaguchi, Kuniaki Sato, Taro Tobo, Hidenari Hirata, Yosuke Kuroda, Sho Nambara, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Takahiro Ochiya, Katsuhiko Yanaga, Satoru Miyano, Koshi Mimori
A primary tumor can create a premetastatic niche in distant organs to facilitate the development of metastasis. The mechanism by which tumor cells communicate with host cells to develop premetastatic niches is unclear. We focused on the role of microRNA (miR) signaling in promoting metastasis. Here, we identified miR-203 as a signaling molecule between tumors and monocytes in metastatic colorectal cancer (CRC) patients. Notably, high expression of serum exosomal miR-203, a major form in circulation, was associated with distant metastasis and an independent poor prognostic factor, whereas low expression in tumor tissues was a poor prognostic factor in CRC patients...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108215/-research-advances-in-the-role-of-mesenchymal-stem-cells-and-their-exosomes-in-treatment-of-liver-diseases
#14
W H Niu, J J Zhang, Z Y Zhu
At present, liver transplantation remains the most effective treatment for acute liver failure and advanced cirrhosis, but its use and promotion are limited by insufficient organ donors, financial consideration, and requirements for lifelong immunosuppression. In recent years, stem cell transplantation has been recommended as an effective substitutive therapy for liver disease. Mesenchymal stem cells, also known as pluripotent interstitial stromal cells, are self-renewing cells that can be found in almost all postnatal organs and tissues, including the liver...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29069781/downregulation-of-circulating-exosomal-mir-638-predicts-poor-prognosis-in-colon-cancer-patients
#15
Shushan Yan, Guangwang Dang, Xiaoyu Zhang, Chengwen Jin, Lang Qin, Yugang Wang, Min Shi, Haijin Huang, Quanhong Duan
Exosome-encapsulated microRNAs have been recognized as novel and stable biomarkers for cancer. However, little is known about the role of exosomal microRNAs in colon cancer. In the present study, we investigated the expression of serous exosomal microRNA-638 (miR-638) and its prognostic effect in patients with colon cancer. Serous exosomal samples were assayed by quantitative real-time PCR. Kaplan-Meier analysis was adopted to determine the overall survival (OS) and disease-free survival (DFS) of colon cancer patients...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063370/pathways-of-production-and-delivery-of-hepatocyte-exosomes
#16
Li Chen, Ruju Chen, Sherri Kemper, David R Brigstock
Hepatocyte exosomes (Exo(Hep)) are proposed to mediate physiological or pathophysiological signaling in a variety of hepatic target cells. Exo(Hep) were purified from the medium of primary mouse hepatocytes or AML12 cells and characterized as ~100 nm nanovesicles that were positive for proteins commonly found in exosomes (CD9, CD81, flotillin) or hepatocytes (asialoglycoprotein receptor). Ethanol treatment of hepatocytes caused increased Exo(Hep) release and increased cellular mRNA expression of components involved in intracellular vesicle trafficking (Rab 5a,b,c, Rab 7a, Rab 27a,b) or exosome biogenesis via the ESCRT (HGS, Alix, STAM1, TSG101, VTA1, YKT6) or ceramide (nSmase2) pathways...
October 23, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29029277/mir-122-release-in-exosomes-precedes-overt-tolvaptan-induced-necrosis-in-a-primary-human-hepatocyte-micropatterned-coculture-model
#17
Merrie Mosedale, J Scott Eaddy, O Joseph Trask, Natalie S Holman, Kristina K Wolf, Edward LeCluyse, Brenton R Ware, Salman R Khetani, Jingtao Lu, William J Brock, Sharin E Roth, Paul B Watkins
Idiosyncratic drug-induced liver injury (IDILI) is thought to often result from an adaptive immune attack on the liver. However, it has been proposed that the cascade of events culminating in an adaptive immune response begins with drug-induced hepatocyte stress, release of exosomal danger signals, and innate immune activation, all of which may occur in the absence of significant hepatocelluar death. A micropatterned coculture model (HepatoPac®) was used to explore the possibility that changes in exosome content precede overt necrosis in response to the IDILI drug tolvaptan...
September 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29023935/exosome-mir-335-as-a-novel-therapeutic-strategy-in-hepatocellular-carcinoma
#18
Fang Wang, Tian Hongwei, Ling Li, Klaus Piontek, Masazumi Sakaguchi, Florin M Selaru
Hepatocellular Cancer (HCC) is a common and deadly cancer. Most cases of HCC arise in a cirrhotic/fibrotic liver, raising the possibility that the environment plays a paramount role in cancer genesis. Previous studies from our group and others have shown that, in desmoplastic cancers, there is a rich intercellular communication between activated, cancer-associated fibroblasts (CAF) and cancer cells. Moreover, Extracellular Vesicles (EVs), or exosomes, were identified asan important arm of this intercellular communication platform...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28969005/pancreatic-cancer-derived-exosomes-promote-tumor-metastasis-and-liver-pre-metastatic-niche-formation
#19
Zeqian Yu, Susu Zhao, Long Ren, Lishan Wang, Zhangjun Chen, Robert M Hoffman, Jiahua Zhou
Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells in vitro. Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis in vivo...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28947960/exosome-encapsulated-micrornas-as-circulating-biomarkers-for-colorectal-cancer
#20
Shushan Yan, Bing Han, Shunyuan Gao, Xiaochen Wang, Zengfang Wang, Fakai Wang, Jianjun Zhang, Donghua Xu, Beicheng Sun
Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed...
September 1, 2017: Oncotarget
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