Journal ArticleDOI
Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components
Hong Ji,David W. Greening,Thomas W. Barnes,Justin Wee Eng Lim,Bow J. Tauro,Bow J. Tauro,Alin Rai,Rong Xu,Christopher G. Adda,Suresh Mathivanan,Wei Zhao,Yanhong Xue,Tao Xu,Hong-Jian Zhu,Richard J. Simpson +14 more
TLDR
The selective enrichment of metastatic factors and signaling pathway components in metastatic colon cancer cell‐derived exosomes contributes to the understanding of the cross‐talk between tumor and stromal cells in the tumor microenvironment.Abstract:
Exosomes are small extracellular 40-100 nm diameter membrane vesicles of late endosomal origin that can mediate intercellular transfer of RNAs and proteins to assist premetastatic niche formation. Using primary (SW480) and metastatic (SW620) human isogenic colorectal cancer cell lines we compared exosome protein profiles to yield valuable insights into metastatic factors and signaling molecules fundamental to tumor progression. Exosomes purified using OptiPrep™ density gradient fractionation were 40-100 nm in diameter, were of a buoyant density ~1.09 g/mL, and displayed stereotypic exosomal markers TSG101, Alix, and CD63. A major finding was the selective enrichment of metastatic factors (MET, S100A8, S100A9, TNC), signal transduction molecules (EFNB2, JAG1, SRC, TNIK), and lipid raft and lipid raft-associated components (CAV1, FLOT1, FLOT2, PROM1) in exosomes derived from metastatic SW620 cells. Additionally, using cryo-electron microscopy, ultrastructural components in exosomes were identified. A key finding of this study was the detection and colocalization of protein complexes EPCAM-CLDN7 and TNIK-RAP2A in colorectal cancer cell exosomes. The selective enrichment of metastatic factors and signaling pathway components in metastatic colon cancer cell-derived exosomes contributes to our understanding of the cross-talk between tumor and stromal cells in the tumor microenvironment.read more
Citations
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Journal ArticleDOI
Extracellular vesicles in cancer - implications for future improvements in cancer care.
TL;DR: A review of the biophysical properties and physiological functions of extracellular vesicles, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics can be found in this paper.
Journal ArticleDOI
The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling
Jan Van Deun,Pieter Mestdagh,Raija Sormunen,Veronique Cocquyt,Karim Vermaelen,Jo Vandesompele,Marc Bracke,Olivier De Wever,An Hendrix +8 more
TL;DR: OptiPrep density gradient centrifugation outperforms ultracentrifugation and ExoQuick and Total Exosome Isolation precipitation in terms of purity, and the purest exosome fractions reveal a unique mRNA profile enriched for translation, ribosome, mitochondrion and nuclear lumen function.
Journal ArticleDOI
Extracellular vesicle isolation and characterization: toward clinical application
Rong Xu,David W. Greening,Hong-Jian Zhu,Nobuhiro Takahashi,Richard J. Simpson,Richard J. Simpson +5 more
TL;DR: The nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs are discussed, as well as various applications of EVs in clinical diagnosis.
Journal ArticleDOI
Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
Ayuko Hoshino,Ayuko Hoshino,Han Sang Kim,Han Sang Kim,Linda Bojmar,Linda Bojmar,Linda Bojmar,Kofi Ennu Gyan,Michele Cioffi,Jonathan M. Hernandez,Jonathan M. Hernandez,Jonathan M. Hernandez,Constantinos P. Zambirinis,Constantinos P. Zambirinis,Gonçalo Rodrigues,Gonçalo Rodrigues,Henrik Molina,Søren Heissel,Milica Tesic Mark,Loïc Steiner,Loïc Steiner,Alberto Benito-Martin,Serena Lucotti,Angela Di Giannatale,Katharine Offer,Miho Nakajima,Caitlin Williams,Laura Nogués,Laura Nogués,Fanny A. Pelissier Vatter,Ayako Hashimoto,Ayako Hashimoto,Ayako Hashimoto,Alexander E. Davies,Daniela Freitas,Daniela Freitas,Candia M. Kenific,Yonathan Ararso,Weston Buehring,Pernille Lauritzen,Yusuke Ogitani,Kei Sugiura,Kei Sugiura,Naoko Takahashi,Maša Alečković,Kayleen A. Bailey,Joshua S. Jolissant,Joshua S. Jolissant,Huajuan Wang,Ashton Harris,L. Miles Schaeffer,Guillermo García-Santos,Guillermo García-Santos,Zoe Posner,Vinod P. Balachandran,Yasmin Khakoo,G. Praveen Raju,Avigdor Scherz,Irit Sagi,Ruth Scherz-Shouval,Yosef Yarden,Moshe Oren,Mahathi Malladi,Mary Petriccione,Kevin C. De Braganca,Maria Donzelli,Cheryl Fischer,Stephanie Vitolano,Geraldine P. Wright,Lee Ganshaw,Mariel Marrano,Amina Ahmed,Joe DeStefano,Enrico Danzer,Michael H.A. Roehrl,Norman J. Lacayo,Theresa C. Vincent,Theresa C. Vincent,Martin R. Weiser,Mary S. Brady,Paul A. Meyers,Leonard H. Wexler,Srikanth R. Ambati,Alexander J. Chou,Emily K. Slotkin,Shakeel Modak,Stephen S. Roberts,Ellen M. Basu,Daniel Diolaiti,Benjamin A. Krantz,Benjamin A. Krantz,Fatima Cardoso,Amber L. Simpson,Michael F. Berger,Charles M. Rudin,Diane M. Simeone,Maneesh Jain,Cyrus M. Ghajar,Surinder K. Batra,Ben Z. Stanger,Jack D. Bui,Kristy A. Brown,Vinagolu K. Rajasekhar,John H. Healey,Maria de Sousa,Maria de Sousa,Kim Kramer,Sujit Sheth,Jeanine Baisch,Virginia Pascual,Todd E. Heaton,Michael P. La Quaglia,David J. Pisapia,Robert E. Schwartz,Haiying Zhang,Yuan Liu,Arti Shukla,Laurence Blavier,Yves A. DeClerck,Mark A. LaBarge,Mina J. Bissell,Thomas C. Caffrey,Paul M. Grandgenett,Michael A. Hollingsworth,Jacqueline Bromberg,Jacqueline Bromberg,Bruno Costa-Silva,Héctor Peinado,Yibin Kang,Benjamin A. Garcia,Eileen M. O'Reilly,David P. Kelsen,Tanya M. Trippett,David R. Jones,Irina Matei,William R. Jarnagin,David Lyden +136 more
TL;DR: EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type, and a panel of tumor-type-specific EVP proteins in TEs and plasma are defined, which can classify tumors of unknown primary origin.
Book ChapterDOI
A Protocol for Exosome Isolation and Characterization: Evaluation of Ultracentrifugation, Density-Gradient Separation, and Immunoaffinity Capture Methods
TL;DR: This chapter reveals the protocol and key insights into the isolation, purification and characterization of exosomes, distinct from shed microvesicles and apoptotic blebs, and concludes that density-based separation (DG-Exos) provides significant advantages for exosome isolation when the use of immunoaffinity capture is limited.
References
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Journal ArticleDOI
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
TL;DR: It is shown that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location, and it is proposed that this RNA is called “exosomal shuttle RNA” (esRNA).
Journal ArticleDOI
UniProt: the Universal Protein knowledgebase
Rolf Apweiler,Amos Marc Bairoch,Cathy H. Wu,Winona C. Barker,Brigitte Boeckmann,Serenella Ferro,Elisabeth Gasteiger,Hongzhan Huang,Rodrigo Lopez,Michele Magrane,Maria Jesus Martin,Darren A. Natale,Claire O'Donovan,Nicole Redaschi,Lai-Su L. Yeh +14 more
TL;DR: The Swiss-Prot, TrEMBL and PIR protein database activities have united to form the Universal Protein Knowledgebase (UniProt), which is to provide a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and query interfaces.
Journal ArticleDOI
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.
Journal ArticleDOI
NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins
TL;DR: The National Center for Biotechnology Information Reference Sequence (RefSeq) database provides a non-redundant collection of sequences representing genomic data, transcripts and proteins that pragmatically includes sequence data that are currently publicly available in the archival databases.
Journal ArticleDOI
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.
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