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Glioma AND exosome

Mark Katakowski, Michael Chopp
Exosomes are small microvesicles released by cells that efficiently transfer their molecular cargo to other cells, including tumor. Exosomes may pass the blood-brain barrier and have been demonstrated to deliver RNAs contained within to brain. As they are non-viable, the risk profile of exosomes is thought to be less than that of cellular therapies. Exosomes can be manufactured at scale in culture, and exosomes can be engineered to incorporate therapeutic miRNAs, siRNAs, or chemotherapeutic molecules. As natural biological delivery vehicles, interest in the use of exosomes as therapeutic delivery agents is growing...
April 2016: Cellular and Molecular Neurobiology
J Bryan Iorgulescu, Michael E Ivan, Michael Safaee, Andrew T Parsa
Tumor-derived microvesicular exosomes permit intercellular communication both locally and systemically by delivering a snapshot of the tumor cell's constituents. We thus investigated whether exosomes mediate malignant glioma's facility for inducing peripheral immunosuppression. In Western blot and RT-PCR analyses, glioma-derived exosomes displayed exosome-specific markers, but failed to recapitulate the antigen-presentation machinery, surface co-modulatory signals, or immunosuppressive mediator status of their parent tumor cells...
January 15, 2016: Journal of Neuroimmunology
Rajshekhar A Kore, Edathara C Abraham
Exosomes mediate secretion of crystallin alphaB (cryAB), a well characterized molecular chaperone with anti-apoptotic activity. However, the mechanisms governing its packaging and secretion remained unexplored. In glioma cells, notwithstanding extensive phosphorylation of cryAB at Ser59 followed by Ser45 (Ser19 is largely unphosphorylated), we discovered that the majority of secreted exosomal cryAB is nonphosphorylated. Transient ectopic expression of a yellow fluorescent protein (YFP) tagged triple phosphomimic (3-SD) cryAB construct in cryAB absent glioma cells led to the formation of large cytosolic inclusions...
February 2016: Biochimica et Biophysica Acta
Rui Shi, Pei-Yin Wang, Xin-Yi Li, Jian-Xin Chen, Yan Li, Xin-Zhong Zhang, Chen-Guang Zhang, Tao Jiang, Wen-Bin Li, Wei Ding, Shu-Jun Cheng
Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome-contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group...
September 29, 2015: Oncotarget
Xuebing Ding, Mingming Ma, Junfang Teng, Robert K F Teng, Shuang Zhou, Jingzheng Yin, Ekokobe Fonkem, Jason H Huang, Erxi Wu, Xuejing Wang
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a continuum of devastating neurodegenerative diseases, characterized by transactive response DNA-binding protein of 43 kDa (TDP-43) aggregates accumulation throughout the nervous system. Despite rapidly emerging evidence suggesting the hypothesis of 'prion-like propagation' of TDP-43 positive inclusion in the regional spread of ALS symptoms, whether and how TDP-43 aggregates spread between cells is not clear. Herein, we established a cerebrospinal fluid (CSF)-cultured cell model to dissect mechanisms governing TDP-43 aggregates formation and propagation...
September 15, 2015: Oncotarget
Kirsten Ridder, Alexandra Sevko, Janina Heide, Maria Dams, Anne-Kathleen Rupp, Jadranka Macas, Julia Starmann, Marc Tjwa, Karl H Plate, Holger Sültmann, Peter Altevogt, Viktor Umansky, Stefan Momma
Extracellular vesicles (EVs) have been shown to transfer various molecules, including functional RNA between cells and this process has been suggested to be particularly relevant in tumor-host interactions. However, data on EV-mediated RNA transfer has been obtained primarily by in vitro experiments or involving ex vivo manipulations likely affecting its biology, leaving their physiological relevance unclear. We engineered glioma and carcinoma tumor cells to express Cre recombinase showing their release of EVs containing Cre mRNA in various EV subfractions including exosomes...
June 2015: Oncoimmunology
Laurent Muller, Sylvia Muller-Haegele, Masato Mitsuhashi, William Gooding, Hideho Okada, Theresa L Whiteside
Exosomes in plasma of glioma patients hold promise as biomarkers of prognosis. We aimed to determine whether changes in total exosomal protein and mRNA expression levels could serve as surrogate markers of immunological and clinical responses in glioma patients receiving antitumor vaccines. Exosomes were isolated from pre/post-vaccine plasma specimens in 20/22 patients enrolled in a phase I/II trial with the antitumor vaccine. Exosomal protein content was analyzed and mRNA expression levels for 24 genes were simultaneously assessed by qRT-PCR...
June 2015: Oncoimmunology
Ichiro Nakano, Delphine Garnier, Mutsuko Minata, Janusz Rak
Extracellular vesicles (EVs) act as carriers of molecular and oncogenic signatures present in subsets of tumour cells and tumour-associated stroma, and as mediators of intercellular communication. These processes likely involve cancer stem cells (CSCs). EVs represent a unique pathway of cellular export and cell-to-cell transfer of insoluble molecular regulators such as membrane receptors, signalling proteins and metabolites, thereby influencing the functional integration of cancer cell populations. While mechanisms that control biogenesis, cargo and uptake of different classes of EVs (exosomes, microvesicles, ectosomes, large oncosomes) are poorly understood, they likely remain under the influence of stress-responses, microenvironment and oncogenic processes that define the biology and heterogeneity of human cancers...
April 2015: Seminars in Cell & Developmental Biology
Ning Bu, Haiqin Wu, Guilian Zhang, Shuqin Zhan, Ru Zhang, Hong Sun, Yun Du, Li Yao, Huqing Wang
Chaperone-rich cell lysates (CRCLs) may play an important role in the development of anti-tumor vaccines. Tumor-derived CRCLs have been reported to activate dendritic cells (DCs) to elicit potent anti-tumor activity. However, the role of DC-derived exosomes (DEXs) secreted from DCs loaded with CRCLs in the treatment of tumors has not been clearly determined. In the present study, DEXs were generated from DCs loaded with CRCLs derived from GL261 glioma cells. These DEXs, designated DEX (CRCL-GL261), were then used to treat DCs to create DEX (CRCL-GL261)-DCs...
July 2015: Journal of Molecular Neuroscience: MN
Andrea Del Fattore, Rosa Luciano, Rossana Saracino, Giulia Battafarano, Cristiano Rizzo, Luisa Pascucci, Giulio Alessandri, Augusto Pessina, Antonio Perrotta, Alessandra Fierabracci, Maurizio Muraca
BACKGROUND: Malignant glial tumors, including glioblastoma multiforme, account for 15 - 20% of pediatric CNS malignancies. They are most resistant to therapy and are associated with a poor prognosis. OBJECTIVE: Given the ability of mesenchymal stem cells (MSCs) to affect glioma growth, we investigated the effects of extracellular vesicles (EVs) derived from MSCs on U87MG glioblastoma cells line. METHODS: EVs were isolated from culture media of MSCs from different sources, including bone marrow (BM), umbilical cord (UC) and adipose tissue (AT) and added to U87MG culture...
April 2015: Expert Opinion on Biological Therapy
Ning Bu, Haiqin Wu, Guilian Zhang, Xiaoling Ma, Ping Zhao, Nina Zhai, Li Xiang, Huifang Cao, Xinli Yang, Jingjie Liu
Dendritic cells (DCs) pulsed with exosomes can stimulate efficient cytotoxic T-lymphocyte responses and anti-tumor immunity. However, the quantity of DC-derived exosomes (DCex) obtained from various culture systems is very low, which is a significant practical issue hampering progress in this research area and needs to be addressed. Gliomas were particularly aggressive, with high morbidity and mortality, indicating that this is a form of incurable highly malignant tumor of the brain with poor prognosis. In the present study, we demonstrate that the CELLine 1000 culture system can dramatically increase the production of DCex...
January 2, 2015: Biochemical and Biophysical Research Communications
Song Han, Sizhe Feng, Mingliang Ren, Enlong Ma, Xiaonan Wang, Lunshan Xu, Minhui Xu
Tumor specific immune regulatory cells play an important role in the pathogenesis of glioma. The mechanisms have not been fully understood yet. It is suggested that placenta growth factor (PlGF) is involved in the generation of immune regulatory cells. This study aims to investigate the role of glioma cell-derived PlGF in the generation of regulatory B cells (Breg). Glioma cells were isolated from surgically removed glioma tissue. Cytokines were measured by enzyme-linked immunosorbent assay, quantitative real time RT-PCR and Western blotting...
December 2014: International Journal of Biochemistry & Cell Biology
Larry A Harshyne, Kirsten M Hooper, Edward G Andrews, Brian J Nasca, Lawrence C Kenyon, David W Andrews, D Craig Hooper
Glioblastomas are primary intracranial tumors for which there is no cure. Patients receiving standard of care, chemotherapy and irradiation, survive approximately 15 months prompting studies of alternative therapies including vaccination. In a pilot study, a vaccine consisting of Lucite diffusion chambers containing irradiated autologous tumor cells pre-treated with an antisense oligodeoxynucleotide (AS-ODN) directed against the insulin-like growth factor type 1 receptor was found to elicit positive clinical responses in 8/12 patients when implanted in the rectus sheath for 24 h...
March 2015: Cancer Immunology, Immunotherapy: CII
Rajshekhar A Kore, Edathara C Abraham
In the brain, levels of inflammatory cytokines, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), are elevated under traumatic brain injury, neuroinflammatory conditions and glioblastoma multiforme (GBM). In GBM, the levels of small heat shock protein, CRYAB (HspB5) are also reported to be elevated, where it has been shown to exert anti-apoptotic activity. Interestingly, CRYAB is secreted via exosomes by various cells. In order to understand the relation between inflammatory cytokines and CRYAB, U373 glioma cells, were stimulated with proinflammatory cytokines, IL-1β and TNF-α, and their effect on CRYAB levels in cells and secreted exosomes was studied...
October 24, 2014: Biochemical and Biophysical Research Communications
Johan M Kros, Dana M Mustafa, Lennard J M Dekker, Peter A E Sillevis Smitt, Theo M Luider, Ping-Pin Zheng
Validated biomarkers for patients suffering from gliomas are urgently needed for standardizing measurements of the effects of treatment in daily clinical practice and trials. Circulating body fluids offer easily accessible sources for such markers. This review highlights various categories of tumor-associated circulating biomarkers identified in blood and cerebrospinal fluid of glioma patients, including circulating tumor cells, exosomes, nucleic acids, proteins, and oncometabolites. The validation and potential clinical utility of these biomarkers is briefly discussed...
March 2015: Neuro-oncology
Dimitry A Chistiakov, Vladimir P Chekhonin
Extracellular vesicles (EVs) are commonly used by normal and tumor cells for communication at long distances to exchange by complex molecular messages and deliver a variety of essential biomolecules. EVs (exosomes and microvesicles) released in large numbers by glioma cells represent a key mechanism of intercellular signaling. Tumor-derived EVs are produced to regulate all vital functions of tumor cells including growth, proliferation, migration, survival, malignancy, invasion, and resistance to host anti-tumor immunity and anti-cancer drugs...
September 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jong Hyuk Yoon, Jaeyoon Kim, Kyung Lock Kim, Do-Hyeon Kim, Sun-Ju Jung, Hyeongjoo Lee, Jaewang Ghim, Dayea Kim, Jong Bae Park, Sung Ho Ryu, Taehoon G Lee
High-grade gliomas are one of the most common brain tumors and notorious for poor prognosis due to their malignant nature. Gliomas have an extensive area of hypoxia, which is critical for glioma progression by inducing aggressiveness and activating the angiogenesis process in the tumor microenvironment. To resolve the factors responsible for the highly malignant nature of gliomas, we comprehensively profiled the U373MG glioma cell secretome-exosome and soluble fraction under hypoxic and normoxic conditions...
June 2014: Proteomics
Evgenia Bourkoula, Damiano Mangoni, Tamara Ius, Anja Pucer, Miriam Isola, Daniela Musiello, Stefania Marzinotto, Barbara Toffoletto, Marisa Sorrentino, Anita Palma, Federica Caponnetto, Giorgia Gregoraci, Marco Vindigni, Stefano Pizzolitto, Giovanni Falconieri, Giovanna De Maglio, Vanna Pecile, Maria Elisabetta Ruaro, Giorgia Gri, Pietro Parisse, Loredana Casalis, Giacinto Scoles, Miran Skrap, Carlo Alberto Beltrami, Antonio Paolo Beltrami, Daniela Cesselli
BACKGROUND: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm...
May 2014: Stem Cells
Niken M Mahaweni, Margaretha E H Kaijen-Lambers, Jacqueline Dekkers, Joachim G J V Aerts, Joost P J J Hegmans
BACKGROUND: In 2001, it was postulated that tumour-derived exosomes could be a potent source of tumour-associated antigens (TAA). Since then, much knowledge is gained on their role in tumorigenesis but only very recently tumour-derived exosomes were used in dendritic cell (DC)-based immunotherapy. For this, DCs were cultured ex-vivo and loaded with exosomes derived from immunogenic tumours such as melanoma or glioma and re-administrated to induce anti-tumour responses in primary and metastatic tumour mouse models...
2013: Journal of Extracellular Vesicles
Cheryl C Y Li, Sally A Eaton, Paul E Young, Maggie Lee, Rupert Shuttleworth, David T Humphreys, Georges E Grau, Valery Combes, Mary Bebawy, Joyce Gong, Susan Brammah, Michael E Buckland, Catherine M Suter
Interactions between glioma cells and their local environment are critical determinants of brain tumor growth, infiltration and neovascularisation. Communication with host cells and stroma via microvesicles represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. Here we have taken an unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells. We find that glioma microvesicles are predominantly of exosomal origin and contain complex populations of coding and noncoding RNAs in proportions that are distinct from those in the cells from which they are derived...
August 2013: RNA Biology
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