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Exosome AND cancer

Takeshi Harada, Hideki Yamamoto, Shosei Kishida, Michiko Kishida, Chihiro Awada, Toshifumi Takao, Akira Kikuchi
Wnt5b, a member of the same family of proteins as Wnt5a of which overexpression is associated with cancer aggressiveness, is suggested to be involved in cancer progression, however details remain unclarified. We analyzed biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b are essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a...
October 20, 2016: Cancer Science
Tomasz Róg, Adam Orłowski, Alicia Llorente, Tore Skotland, Tuulia Sylvänne, Dimple Kauhanen, Kim Ekroos, Kirsten Sandvig, Ilpo Vattulainen
In this Data in Brief article we provide a data package of GROMACS input files for atomistic molecular dynamics simulations of multicomponent, asymmetric lipid bilayers using the OPLS-AA force field. These data include 14 model bilayers composed of 8 different lipid molecules. The lipids present in these models are: cholesterol (CHOL), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (POPE), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphatidyl-ethanolamine (SOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (SOPS), N-palmitoyl-D-erythro-sphingosyl-phosphatidylcholine (SM16), and N-lignoceroyl-D-erythro-sphingosyl-phosphatidylcholine (SM24)...
June 2016: Data in Brief
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
Jamal El-Saghir, Farah Nassar, Nadim Tawil, Marwan El-Sabban
BACKGROUND: Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia...
October 19, 2016: Retrovirology
Koji Nakamura, Kenjiro Sawada, Yasuto Kinose, Akihiko Yoshimura, Aska Toda, Erika Nakatsuka, Kae Hashimoto, Seiji Mabuchi, Ken-Ichirou Morishige, Hirohisa Kurachi, Ernst Lengyel, Tadashi Kimura
: Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMCs) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications are exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs...
October 6, 2016: Molecular Cancer Research: MCR
Ralph D Sanderson, Michael Elkin, Alan C Rapraeger, Neta Ilan, Israel Vlodavsky
Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via non-enzymatic mechanisms that directly activate signaling at the cell surface...
October 18, 2016: FEBS Journal
Zebo Huang, Danxia Zhu, Lirong Wu, Mingfeng He, Xin Zhou, Lan Zhang, Huo Zhang, Weiwei Wang, Jun Zhu, Wenfang Cheng, Yan Chen, Yong Fan, Lianwen Qi, Yin Yin, Wei Zhu, Yongqian Shu, Ping Liu
BACKGROUND: Circulating microRNAs (miRNAs) in serum may serve as promising diagnostic biomarkers for patients with gastric cancer (GC). METHODS: Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel, we identified 58 differentially expressed miRNAs from 3 GC pool samples and 1 normal control (NC) pool in the initial screening phase. Identified miRNAs were further validated in the training (49 GC VS. 47 NCs) and validation phases (154 GC VS...
October 18, 2016: Cancer Epidemiology, Biomarkers & Prevention
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
Jin Cai, Gengze Wu, Pedro A Jose, Chunyu Zeng
Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs...
October 14, 2016: Experimental Cell Research
Jin Lin, Yan Wang, Ye-Qing Zou, Xin Chen, Bo Huang, Jing Liu, Yan-Mei Xu, Jing Li, Jing Zhang, Wei-Ming Yang, Qing-Hua Min, Fan Sun, Shu-Qi Li, Qiu-Fang Gao, Xiao-Zhong Wang
MicroRNAs (miRNAs) have been found to play important regulatory roles in various physiological and pathological processes. MiRNAs also exhibit high stability and are present at high concentrations in human bodily fluids. Consequently, miRNAs may represent attractive and novel diagnostic biomarkers for certain clinical conditions. Recently, the capacity for extracellular vesicles, including microvesicles and exosomes, to carry miRNAs that participate in cell-to-cell communication has been described. In the present study, the miRNA expression patterns for three kinds of pleural effusions that were obtained from patients with pneumonia (group A), pulmonary tuberculosis (group B), and lung cancer (group C) were detected with high-throughput sequencing...
October 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and 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
Pinar Kanlikilicer, Mohammed Saber, Recep Bayraktar, Rahul Mitra, Cristina Ivan, Burcu Aslan, Xinna Zhang, Justyna Filant, Andreia M Silva, Cristian Rodriguez-Aguayo, Emine Bayraktar, Martin Pichler, Bulent Ozpolat, George A Calin, Anil K Sood, Gabriel Lopez-Berestein
Cancer cells actively promote their tumorigenic behavior by reprogramming gene expression. Loading intraluminal vesicles with specific miRNAs and releasing them into the tumor microenvironment as exosomes is one mechanism of reprogramming whose regulation remains to be elucidated. Here, we report that miR-6126 is ubiquitously released in high abundance from both chemosensitive and chemoresistant ovarian cancer cells via exosomes. Overexpression of miR-6126 was confirmed in healthy ovarian tissue compared to ovarian cancer patient samples and correlated with better overall survival in high-grade serous ovarian cancer patients...
October 14, 2016: Cancer Research
Zhaogang Yang, Jing Xie, Jing Zhu, Chen Kang, Chiling Chiang, Xinmei Wang, Xiaobing Wang, Tairong Kuang, Feng Chen, Zhou Chen, Aili Zhang, Bo Yu, Robert J Lee, Lesheng Teng, L James Lee
Exosomes, the smallest subgroup of extracellular vesicles, have been recognized as extracellular organelles that contain genetic and proteomic information for long distance intercellular communication. Exosome-based drug delivery is currently a subject of intensive research. Here, we report a novel strategy to produce nanoscale exosome-mimics (EMs) in sufficient quantity for gene delivery in cancer both in vitro and in vivo. Size-controllable EMs were generated at a high yield by serial extrusion of non-tumorigenic epithelial MCF-10A cells through filters with different pore sizes...
October 11, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Igor Slivac, David Guay, Mathias Mangion, Juliette Champeil, Bruno Gaillet
Delivery of nucleic acid-based molecules in human cells is a highly studied approach for the treatment of several disorders including monogenic diseases and cancers. Non-viral vectors for DNA and RNA transfer, although in general less efficient than virus-based systems, are particularly well adapted mostly due to the absence of biosafety concerns. Non-viral methods could be classified in two main groups: physical and vector-assisted delivery systems. Both groups comprise several different methods, none of them universally applicable...
October 14, 2016: Expert Opinion on Biological Therapy
C M Wong, L A Nash, J Del Papa, K L Poulin, T Falls, J C Bell, R J Parks
When injected directly into a tumor mass, adenovirus (Ad) vectors only transduce cells immediately along the injection tract. Expression of fusogenic proteins from the Ad vector can lead to syncytium formation, which efficiently spreads the therapeutic effect. Fusogenic proteins can also cause cancer cell death directly, and enhance the release of exosome-like particles containing tumor-associated antigens, which boosts the anti-tumor immune response. In this study, we have examined whether delivery of an early region 1 (E1)-deleted, replication-defective Ad vector encoding the reptilian reovirus p14 fusion-associated small transmembrane (FAST) protein can provide therapeutic efficacy in an immunocompetent mouse tumor model...
October 14, 2016: Cancer Gene Therapy
Marzia Del Re, Elisa Biasco, Stefania Crucitta, Lisa Derosa, Eleonora Rofi, Cinzia Orlandini, Mario Miccoli, Luca Galli, Alfredo Falcone, Guido W Jenster, Ron H van Schaik, Romano Danesi
BACKGROUND: The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due to limitations of the methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. OBJECTIVE: To confirm AR-V7 as a predictor of resistance to hormonal therapy and develop a new approach to assess AR-V7 by highly sensitive digital droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA...
August 26, 2016: European Urology
Yusuke Yoshioka, Takahiro Ochiya
Exosomes are membrane vesicles approximately 100 nm in diameter, present in a wide range of body fluids, including blood, cerebrospinal fluid, urine and saliva. Exosomes reflect the physiological state of their cells of origin and cancer cell-derived exosomes carry pathogenic components, such as proteins, messenger RNA (mRNA), microRNA (miRNA), and DNA. Thus, exosomes in body fluids provide a rich source of potential biomarkers. However, the use of exosomes as biomarkers to improve patient care has been limited by their small size and the extensive sample preparation required for their isolation and measurement...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Diego De Miguel, Ana Gallego-Lleyda, José María Ayuso, Dolores Pejenaute-Ochoa, Vidal Jarauta, Isabel Marzo, Luis J Fernández, Ignacio Ochoa, Blanca Conde, Alberto Anel, Luis Martinez-Lostao
During the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials...
October 8, 2016: Cancer Letters
Aihua Hou, Kai Pong Law, Min Qi Tin, Yoon Pin Lim, Louis Tong
Pterygium is a triangular shaped ocular fibrous surface lesion growing from conjunctiva towards central cornea, causing ocular irritation, astigmatism, and visual disturbance. The condition is characterized by epithelial proliferation, fibrovascular growth, chronic inflammation, and prominent extracellular matrix remodeling. Studies have suggested that aberrant extracellular proteins secreted by fibroblasts lead to abnormal matrix production and tissue invasion contributing to the development of the disease...
October 7, 2016: Experimental Eye Research
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