Exosomes impact survival to radiation exposure in cell line models of nervous system cancer.
Oliver D. Mrowczynski,A. B. Madhankumar,Jeffrey M. Sundstrom,Yuanjun Zhao,Yuka Imamura Kawasawa,Becky Slagle-Webb,Christine Mau,Russell Payne,Elias Rizk,Brad E. Zacharia,James R. Connor +10 more
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TLDR
A novel exosome-based mechanism that may underlie a cancer cell's ability to survive radiation is identified that is inhibited induction of proliferation and cellular survival.Abstract:
Radiation is utilized in the therapy of more than 50% of cancer patients. Unfortunately, many malignancies become resistant to radiation over time. We investigated the hypothesis that one method of a cancer cell's ability to survive radiation occurs through cellular communication via exosomes. Exosomes are cell-derived vesicles containing DNA, RNA, and protein. Three properties were analyzed: 1) exosome function, 2) exosome profile and 3) exosome uptake/blockade. To analyze exosome function, we show radiation-derived exosomes increased proliferation and enabled recipient cancer cells to survive radiation in vitro. Furthermore, radiation-derived exosomes increased tumor burden and decreased survival in an in vivo model. To address the mechanism underlying the alterations by exosomes in recipient cells, we obtained a profile of radiation-derived exosomes that showed expression changes favoring a resistant/proliferative profile. Radiation-derived exosomes contain elevated oncogenic miR-889, oncogenic mRNAs, and proteins of the proteasome pathway, Notch, Jak-STAT, and cell cycle pathways. Radiation-derived exosomes contain decreased levels of tumor-suppressive miR-516, miR-365, and multiple tumor-suppressive mRNAs. Ingenuity pathway analysis revealed the most represented networks included cell cycle, growth/survival. Upregulation of DNM2 correlated with increased exosome uptake. To analyze the property of exosome blockade, heparin and simvastatin were used to inhibit uptake of exosomes in recipient cells resulting in inhibited induction of proliferation and cellular survival. Because these agents have shown some success as cancer therapies, our data suggest their mechanism of action could be limiting exosome communication between cells. The results of our study identify a novel exosome-based mechanism that may underlie a cancer cell's ability to survive radiation.read more
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Inflammatory microenvironment remodelling by tumour cells after radiotherapy.
Martin McLaughlin,Emmanuel C Patin,Malin Pedersen,Anna Wilkins,Magnus T. Dillon,Magnus T. Dillon,Alan Melcher,Alan Melcher,Kevin J. Harrington,Kevin J. Harrington +9 more
TL;DR: How radiotherapy, through its immunomodulating effects, represents a promising combination partner with ICIs and how DNA damage response inhibitors in combination with radiotherapy may be used to further augment this approach are described.
Journal ArticleDOI
Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.
Ebrahim Afshinnekoo,Ryan T. Scott,Matthew MacKay,Eloise Pariset,Eloise Pariset,Egle Cekanaviciute,Richard Barker,Simon Gilroy,Duane C. Hassane,Scott M. Smith,Sara R. Zwart,Mayra Nelman-Gonzalez,Brian Crucian,S. A. Ponomarev,Oleg Orlov,Dai Shiba,Masafumi Muratani,Masayuki Yamamoto,Stephanie E. Richards,Parag Vaishampayan,Cem Meydan,Jonathan Foox,Jacqueline Myrrhe,Eric Istasse,Nitin Kumar Singh,Kasthuri Venkateswaran,Jessica A. Keune,Hami E. Ray,Mathias Basner,Jack M. Miller,Jack M. Miller,Martha Hotz Vitaterna,Deanne Taylor,Deanne Taylor,Douglas C. Wallace,Douglas C. Wallace,Kathleen Rubins,Susan M. Bailey,Peter Grabham,Sylvain V. Costes,Christopher E. Mason,Afshin Beheshti,Afshin Beheshti +42 more
TL;DR: The known hazards of human spaceflight are reviewed, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration are discussed.
Journal ArticleDOI
Proteome Profiling of Exosomes Purified from a Small Amount of Human Serum: The Problem of Co-Purified Serum Components.
TL;DR: A simple method of EV isolation from a small amount of human serum using the size-exclusion chromatography (SEC) standalone outperformed other comparable protocols regarding untargeted identification of exosome proteins and could be recommended for pilot exploratory studies when aSmall amount of a serum/plasma specimen is available.
Journal ArticleDOI
Extracellular vesicle-mediated endothelial apoptosis and EV-associated proteins correlate with COVID-19 disease severity.
Balaji Krishnamachary,Christine Cook,Ashok Kumar,Leslie Spikes,Prabhakar Chalise,Navneet K. Dhillon +5 more
TL;DR: In this article, the authors compared the inflammatory and cardiovascular disease-related protein cargo of circulating large and small extracellular vesicles (EVs) from 84 hospitalized patients infected with SARS-CoV-2 with different stages of disease severity.
Journal ArticleDOI
Exosomes in Cancer Radioresistance.
Jie Ni,Joseph Bucci,Joseph Bucci,David Malouf,David Malouf,Matthew C. Knox,Matthew C. Knox,Peter Graham,Peter Graham,Yong Li,Yong Li,Yong Li +11 more
TL;DR: Recent advances in radiation-induced exosome changes in components are discussed, the importance of exosomes in cancer progression and radioresistance for developing novel therapy is emphasized and a new way in radiotherapy and translational medicine is opened.
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Exosomes: composition, biogenesis and function
TL;DR: The physical properties that define exosomes as a specific population of secreted vesicles are described, their biological effects, particularly on the immune system, are summarized, and the potential roles that secretedvesicles could have as intercellular messengers are discussed.
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Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Johan Skog,T. Wurdinger,van Rijn S,Dimphna H. Meijer,Gainche L,Miguel Sena-Esteves,William T. Curry,Bob S. Carter,Anna M. Krichevsky,Xandra O. Breakefield +9 more
TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
Journal ArticleDOI
Tumour exosome integrins determine organotropic metastasis
Ayuko Hoshino,Bruno Costa-Silva,Tang-Long Shen,Gonçalo Rodrigues,Ayako Hashimoto,Milica Tesic Mark,Henrik Molina,Shinji Kohsaka,Angela Di Giannatale,Sophia Ceder,Swarnima Singh,Caitlin Williams,Nadine Soplop,Kunihiro Uryu,Lindsay A. Pharmer,Tari A. King,Linda Bojmar,Alexander E. Davies,Yonathan Ararso,Tuo Zhang,Haiying Zhang,Jonathan M. Hernandez,Joshua Mitchell Weiss,Vanessa D. Dumont-Cole,Kimberly Kramer,Leonard H. Wexler,Aru Narendran,Gary K. Schwartz,John H. Healey,Per Sandström,Knut Jørgen Labori,Elin H. Kure,Paul M. Grandgenett,Michael A. Hollingsworth,Maria de Sousa,Sukwinder Kaur,Maneesh Jain,Kavita Mallya,Surinder K. Batra,William R. Jarnagin,Mary S. Brady,Øystein Fodstad,Volkmar Müller,Klaus Pantel,Andy J. Minn,Mina J. Bissell,Benjamin A. Garcia,Yibin Kang,Yibin Kang,Vinagolu K. Rajasekhar,Cyrus M. Ghajar,Irina Matei,Héctor Peinado,Jacqueline Bromberg,Jacqueline Bromberg,David Lyden +55 more
TL;DR: It is demonstrated that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells.