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Glioma AND exosome

Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, Federica Caponnetto, Ivana Manini, Antonio Paolo Beltrami, Tamara Ius, Miran Skrap, Carla Di Loreto, Giorgia Gri
A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes...
2017: PloS One
Hongsheng Xu, Kezhong Zhang, Hailiang Zong, Ming Shang, Kai Li, Xiaoguang He
Cancer research has revealed the existence of cancer stem cells (CSCs). However, the influence of the surrounding stromal cells present in the microenvironment on CSCs is still poorly understood. The latest studies on gliomas suggested that the microenvironment of human gliomas contains both glioma stem cells (GSCs) and glioma associated (GA)-mesenchymal stem cells (MSCs; (GA-MSCs). Also, studies have suggested that nano- sized vesicles, termed exosomes, have been recently observed to contribute towards intercellular communication within the tumor niche...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Federica Caponnetto, Ivana Manini, Miran Skrap, Timea Palmai-Pallag, Carla Di Loreto, Antonio Paolo Beltrami, Daniela Cesselli, Enrico Ferrari
The ability of exosomes to elicit specific cellular responses suggests that they may be increasingly used as therapeutics. Their vesicular nature makes them suitable as potential nanocarriers for drugs or nucleic acids delivery. Here we address the question whether the method of preparation of enriched exosomal fractions can affect their uptake by cells and their ability to trigger a response. We compared ultracentrifugation and polymer-based precipitation methods on supernatants of glioma-associated stem cells isolated from a high-grade glioma patient...
December 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Noemí García-Romero, Josefa Carrión-Navarro, Susana Esteban-Rubio, Elisa Lázaro-Ibáñez, María Peris-Celda, Marta M Alonso, Juan Guzmán-De-Villoria, Carlos Fernández-Carballal, Ana Ortiz de Mendivil, Sara García-Duque, Carmen Escobedo-Lucea, Ricardo Prat-Acín, Cristóbal Belda-Iniesta, Angel Ayuso-Sacido
Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs-apoptotic bodies, shedding microvesicles and exosomes-cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF)...
January 3, 2017: Oncotarget
Jian-Kai Yang, Ji-Peng Yang, Jing Tong, Shi-Yuan Jing, Bo Fan, Feng Wang, Guo-Zhu Sun, Bao-Hua Jiao
MicroRNA is an important regulator of glioblastoma. This study aims at validating microRNA-221 (miR-221) as a biomarker for glioblastoma, and understanding how miR-221 regulates glioblastoma progression. Using clinical samples, miR-221 expression was analyzed by quantitative reverse-transcriptase PCR (qPCR). SHG-44 cells were treated with anti-miR-221 or U87MG-derived exosomes followed by monitoring changes in cell viability, migration and temozolomide (TMZ) resistance. Bioinformatics approach was used to identify targets of miR-221...
November 11, 2016: Journal of Neuro-oncology
J Gourlay, A P Morokoff, R B Luwor, H-J Zhu, A H Kaye, S S Stylli
Extracellular vesicles (EVs) are known mediators of intercellular communication for both normal and tumour cells. With the capability to transfer nucleic acids, proteins and lipids, EVs are able to influence numerous functional and pathological aspects of both donor and recipient cells. The tumour microenvironment possesses a high level of complex heterogeneity, particularly within the most prominent brain malignancy, glioblastoma multiforme (GBM). This complexity relies on a network-based communication between many different components of the local niche, including the various cell types, stroma, blood vessels, secreted factors and surrounding matrix...
January 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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
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