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Tumor-derived exosomes

Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
Sayantan Maji, Pankaj Chaudhary, Irina Akopova, Phung M Nguyen, Richard J Hare, Ignacy Gryczynski, Jamboor K Vishwanatha
: Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin A2 as one of the most highly expressed proteins in exosomes; however, studies focused on the biological role of exosomal-AnnexinA2 (exo-AnxA2) are still lacking. In this study, mechanistic insight was sought regarding exo-AnxA2 and its function in angiogenesis and breast cancer metastasis. Multiple in vitro and in vivo techniques were used to study the role of exo-AnxA2 in angiogenesis...
October 19, 2016: Molecular Cancer Research: MCR
Shu Wen Wen, Jaclyn Sceneay, Luize G Lima, Christina Sf Wong, Melanie Becker, Sophie Krumeich, Richard J Lobb, Vanessa Castillo, Ke Ni Wong, Sarah Ellis, Belinda S Parker, Andreas Moller
Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here we use optical imaging to determine that exogenously administered fluorescently-labeled exosomes derived from highly metastatic murine breast cancer cells, distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45+ bone marrow-derived cells...
October 19, 2016: Cancer Research
Emilie Duvallet, Mathilde Boulpicante, Takahiro Yamazaki, Chrysoula Daskalogianni, Rodrigo Prado Martins, Sonia Baconnais, Bénédicte Manoury, Robin Fahraeus, Sébastien Apcher
Cellular immune reactions against non-self-epitopes require activation of cytotoxic CD8(+) T-cells via cross-presentation of MHC class I-restricted peptides by professional antigen presenting cells (pAPCs), with the consequent detection and elimination of cells expressing the same antigens via the endogenous (direct) pathway. The source of peptides for the endogenous pathway is constituted of alternative mRNA translation products; however, it is still unclear which source of peptides is used for cross-presentation...
2016: Oncoimmunology
Zhen Wang, Jun-Qiang Chen, Jin-Lu Liu, Lei Tian
Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation...
October 19, 2016: Journal of Translational Medicine
Ioulia Vardaki, Claire Sanchez, Pedro Fonseca, Magnus Olsson, Dimitrios Chioureas, George Rassidakis, Anders Ullén, Boris Zhivotovsky, Magnus Björkholm, Theocharis Panaretakis
The intercellular crosstalk between hematological malignancies and the tumor microenvironment is mediated by cell to cell interactions and soluble factors. One component of the secretome that is gaining increasing attention are the extracellular vesicles and in particular the exosomes. Apart from the role as vectors of molecular information, exosomes have been shown to possess intrinsic biological activity. In this study we have found that caspase-3 is activated in L88 bone marrow stroma cell-derived exosomes and identified one of the substrates to be the anti-apoptotic protein Bcl-xL...
October 14, 2016: Blood
Masaki Morishita, Yuki Takahashi, Akihiro Matsumoto, Makiya Nishikawa, Yoshinobu Takakura
For cancer immunotherapy via tumor antigen vaccination in combination with an adjuvant, major challenges include the identification of a particular tumor antigen and efficient delivery of the antigen as well as adjuvant to antigen-presenting cells. In this study, we proposed an efficient exosome-based tumor antigens-adjuvant co-delivery system using genetically engineered tumor cell-derived exosomes containing endogenous tumor antigens and immunostimulatory CpG DNA. Murine melanoma B16BL6 cells were transfected with a plasmid vector encoding a fusion streptavidin (SAV; a protein that binds to biotin with high affinity)-lactadherin (LA; an exosome-tropic protein) protein, yielding genetically engineered SAV-LA-expressing exosomes (SAV-exo)...
December 2016: Biomaterials
Zhen Qu, Junhua Wu, Junyi Wu, Dongjun Luo, Chunping Jiang, Yitao Ding
BACKGROUND: Exosomes are carriers of intercellular information and regulate the tumor microenvironment. They play an important role in drug resistance by transporting RNA molecules and proteins. However, their effects on sorafenib resistance in hepatocellular carcinoma (HCC) are not completely understood. METHODS: Exosomes were isolated from two invasive hepatoma cell lines (MHCC-97 L and MHCC-97H), and their roles in regulating sorafenib resistance in liver cancer cells as well as the underlying molecular mechanisms were determined...
September 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
October 4, 2016: Oncotarget
Zhe Huang, Yong Feng
Cancer cell-derived exosomes have been actively released into the tumor microenvironment with pleiotropic roles in tumor growth and metastasis, including angiogenesis and immune modulation. However, the functions and underlying mechanisms of exosomes shed by colorectal cancer (CRC) cells under hypoxic conditions remains unknown. Here, we found that exosomes derived from hypoxic CRC cells promoted the proliferation and migration of endothelial cells. Suppression of exosome secretion through RAB27a knockdown in CRC cells inhibited exosomal induced proliferation and migration of endothelial cells...
October 5, 2016: Oncology Research
Abderrahim Benmoussa, Chan Ho C Lee, Benoit Laffont, Patricia Savard, Jonathan Laugier, Eric Boilard, Caroline Gilbert, Ismail Fliss, Patrick Provost
BACKGROUND: MicroRNAs are small, gene-regulatory noncoding RNA species present in large amounts in milk, where they seem to be protected against degradative conditions, presumably because of their association with exosomes. OBJECTIVE: We monitored the relative stability of commercial dairy cow milk microRNAs during digestion and examined their associations with extracellular vesicles (EVs). METHODS: We used a computer-controlled, in vitro, gastrointestinal model TNO intestinal model-1 (TIM-1) and analyzed, by quantitative polymerase chain reaction, the concentration of 2 microRNAs within gastrointestinal tract compartments at different points in time...
October 5, 2016: Journal of Nutrition
Martina Di Modica, Viola Regondi, Marco Sandri, Marilena V Iorio, Adriana Zanetti, Elda Tagliabue, Patrizia Casalini, Tiziana Triulzi
Exosomes-secreted microRNAs play an important role in metastatic spread. During this process breast cancer cells acquire the ability to transmigrate through blood vessels by inducing changes in the endothelial barrier. We focused on miR-939 that is predicted to target VE-cadherin, a component of adherens junction involved in vessel permeability. By in silico analysis miR-939 was found highly expressed in the basal-like tumor subtypes and in our cohort of 63 triple-negative breast cancers (TNBCs) its expression significantly interacted with lymph node status in predicting disease-free survival probability...
September 28, 2016: Cancer Letters
J Diamond, J Chapman, B Ueberheide, S Formenti, S Demaria
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Chen Chen, Shenfei Zong, Zhuyuan Wang, Ju Lu, Dan Zhu, Yizhi Zhang, Yiping Cui
Exosomes are small membrane vesicles secreted by cells and enriched with plenty of proteins. Considering their significant roles in different physical activities and potential value for diagnostic drug delivery, researchers have put great efforts in in vitro tracking and content analysis of exosomes. Recently, the emergence of different kinds of super-resolution microscopy provides powerful tools for exosome study. Here, we demonstrate the application of single-molecule localization based super-resolution imaging technique in the imaging and tracking of cancer-derived exosomes...
October 5, 2016: ACS Applied Materials & Interfaces
Bethany N Hannafon, Yvonne D Trigoso, Cameron L Calloway, Y Daniel Zhao, David H Lum, Alana L Welm, Zhizhuang J Zhao, Kenneth E Blick, William C Dooley, W Q Ding
BACKGROUND: microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin...
2016: Breast Cancer Research: BCR
Noah I Hornick, Ben Doron, Sherif Abdelhamed, Jianya Huan, Christina A Harrington, Rongkun Shen, Xiaolu A Cambronne, Santhosh Chakkaramakkil Verghese, Peter Kurre
Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors. We found that the systemic loss of hematopoietic function is also in part a consequence of AML exosome-directed microRNA (miRNA) trafficking to HSPCs. Exosomes isolated from cultured AML or the plasma from mice bearing AML xenografts exhibited enrichment of miR-150 and miR-155...
September 6, 2016: Science Signaling
Yasunori Matsumoto, Masayuki Kano, Yasunori Akutsu, Naoyuki Hanari, Isamu Hoshino, Kentaro Murakami, Akihiro Usui, Hiroshi Suito, Masahiko Takahashi, Ryota Otsuka, Hu Xin, Aki Komatsu, Keiko Iida, Hisahiro Matsubara
Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established...
September 5, 2016: Oncology Reports
Maria Harmati, Zsofia Tarnai, Gabor Decsi, Sandor Kormondi, Zsolt Szegletes, Laszlo Janovak, Imre Dekany, Okay Saydam, Edina Gyukity-Sebestyen, Gabriella Dobra, Istvan Nagy, Katalin Nagy, Krisztina Buzas
BACKGROUND: Head and neck cancers comprise the sixth most common cancer type worldwide. One of the most remarkable malignancies of the head and neck is the cancer of the nasopharynx, with a strong metastatic tendency already in the early stage. Besides the conventional pathways of metastasis formation, the information content of exosomes produced by the cancer cells may play a key role in metastatic transformation. The aim of this study was to investigate how stressors alter the characteristic of tumor derived exosomes...
September 6, 2016: Journal of Oral Pathology & Medicine
Ming-Chung Jiang
CSE1L (chromosome segregation 1-like protein), also named as CAS (cellular apoptosis susceptibility protein), is highly expressed in most cancer types. CSE1L/CAS is a multiple functional protein that plays roles in apoptosis, cell survival, chromosome assembly, nucleocytoplasmic transport, microvesicle formation, and cancer metastasis; some of the functions are explicitly correlated. CSE1L is also a cancer serum biomarker. The phosphorylation of CAS is regulated by the extracellular signal-regulated kinase (ERK)...
September 5, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kate Nong, Weiwei Wang, Xin Niu, Bin Hu, Chenchao Ma, Yueqing Bai, Bo Wu, Yang Wang, Kaixing Ai
BACKGROUND: This study aimed to evaluate the effect of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury. METHODS: Exosomes were isolated and concentrated from conditioned medium using ultracentrifugation and ultrafiltration. hiPSC-MSCs-Exo were injected systemically via the inferior vena cava in a rat model of 70% warm hepatic I/R injury, and the therapeutic effect was evaluated...
August 31, 2016: Cytotherapy
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