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https://www.readbyqxmd.com/read/30290761/tunneling-nanotubes-evoke-pericyte-endothelial-communication-during-normal-and-tumoral-angiogenesis
#1
Mariella Errede, Domenica Mangieri, Giovanna Longo, Francesco Girolamo, Ignazio de Trizio, Antonella Vimercati, Gabriella Serio, Karl Frei, Roberto Perris, Daniela Virgintino
BACKGROUND: Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex vascularization and collateralization. Here we have investigated the possible presence and the cellular origin of TNTs during normal brain vascularization and also in highly vascularized brain tumors...
October 5, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/30213051/the-significance-of-chondroitin-sulfate-proteoglycan-4-cspg4-in-human-gliomas
#2
REVIEW
Davide Schiffer, Marta Mellai, Renzo Boldorini, Ilaria Bisogno, Silvia Grifoni, Cristiano Corona, Luca Bertero, Paola Cassoni, Cristina Casalone, Laura Annovazzi
Neuron glial antigen 2 (NG2) is a chondroitin sulphate proteoglycan 4 (CSPG4) that occurs in developing and adult central nervous systems (CNSs) as a marker of oligodendrocyte precursor cells (OPCs) together with platelet-derived growth factor receptor α (PDGFRα). It behaves variably in different pathological conditions, and is possibly involved in the origin and progression of human gliomas. In the latter, NG2/CSPG4 induces cell proliferation and migration, is highly expressed in pericytes, and plays a role in neoangiogenesis...
September 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30065025/egfl7-enhances-surface-expression-of-integrin-%C3%AE-5-%C3%AE-1-to-promote-angiogenesis-in-malignant-brain-tumors
#3
Nevenka Dudvarski Stanković, Frank Bicker, Stefanie Keller, David Tw Jones, Patrick N Harter, Arne Kienzle, Clarissa Gillmann, Philipp Arnold, Anna Golebiewska, Olivier Keunen, Alf Giese, Andreas von Deimling, Tobias Bäuerle, Simone P Niclou, Michel Mittelbronn, Weilan Ye, Stefan M Pfister, Mirko H Schmidt
Glioblastoma (GBM) is a typically lethal type of brain tumor with a median survival of 15 months postdiagnosis. This negative prognosis prompted the exploration of alternative treatment options. In particular, the reliance of GBM on angiogenesis triggered the development of anti-VEGF (vascular endothelial growth factor) blocking antibodies such as bevacizumab. Although its application in human GBM only increased progression-free periods but did not improve overall survival, physicians and researchers still utilize this treatment option due to the lack of adequate alternatives...
September 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29876930/enlightenment-of-tumour-vessel-normalization-and-immunotherapy-in-glioblastoma
#4
Lucas Treps
Glioblastoma multiforme (GBM) is a highly vascularized and aggressive brain tumour. Despite aggressive standard care, GBM remains predominantly fatal; hence, new innovative therapies are required. Recent research published in the Journal of Pathology has identified the CGKRK peptide as a promising tool with which to specifically target the tumour vasculature from high-grade glioma. This tumour vessel-homing peptide was fused to the tumour necrosis factor superfamily member LIGHT/TNFSF14, and injected intravenously into murine orthotopic GBM models...
June 7, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29844871/pericytes-vessel-associated-mural-cells-vamcs-are-the-major-source-of-key-epithelial-mesenchymal-transition-emt-factors-slug-and-twist-in-human-glioma
#5
Lisa Mäder, Anna E Blank, David Capper, Janina Jansong, Peter Baumgarten, Naita M Wirsik, Cornelia Zachskorn, Jakob Ehlers, Michael Seifert, Barbara Klink, Stefan Liebner, Simone Niclou, Ulrike Naumann, Patrick N Harter, Michel Mittelbronn
Epithelial-to-mesenchymal transition (EMT) is supposed to be responsible for increased invasion and metastases in epithelial cancer cells. The activation of EMT genes has further been proposed to be important in the process of malignant transformation of primary CNS tumors. Since the cellular source and clinical impact of EMT factors in primary CNS tumors still remain unclear, we aimed at deciphering their distribution in vivo and clinico-pathological relevance in human gliomas. We investigated 350 glioma patients for the expression of the key EMT factors SLUG and TWIST by immunohistochemistry and immunofluorescence related to morpho-genetic alterations such as EGFR -amplification, IDH-1 (R132H) mutation and 1p/19q LOH...
May 8, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761249/targeting-glioblastoma-derived-pericytes-improves-chemotherapeutic-outcome
#6
REVIEW
Daniel A P Guerra, Ana E Paiva, Isadora F G Sena, Patrick O Azevedo, Walison N Silva, Akiva Mintz, Alexander Birbrair
Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival...
May 14, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29736738/glioblastoma-niches-from-the-concept-to-the-phenotypical-reality
#7
Davide Schiffer, Marta Mellai, Enrica Bovio, Ilaria Bisogno, Cristina Casalone, Laura Annovazzi
Recently, the concept of niches as sites of tumor progression, invasion, and angiogenesis in glioblastoma (GB) has been extensively debated. Niches, considered the sites in which glioblastoma stem cells (GSCs) reside, have been classified as perivascular, perinecrotic, and invasive. However, from a neuropathological point of view, it is not easy to establish when a tumor structure can be considered a niche. The relevant literature has been reviewed in the light of our recent experience on the subject. As for perinecrotic niches, the occurrence of GSCs around necrosis is interpreted as triggered by hypoxia through HIF-1α...
May 8, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29713042/endothelial-trans-differentiation-in-glioblastoma-recurring-after-radiotherapy
#8
Ivana De Pascalis, Liliana Morgante, Simone Pacioni, Quintino Giorgio D'Alessandris, Stefano Giannetti, Maurizio Martini, Lucia Ricci-Vitiani, Matteo Malinverno, Elisabetta Dejana, Luigi M Larocca, Roberto Pallini
We hypothesized that in glioblastoma recurring after radiotherapy, a condition whereby the brain endothelium undergoes radiation-induced senescence, tumor cells with endothelial phenotype may be relevant for tumor neovascularization. Matched glioblastoma samples obtained at primary surgery and at surgery for tumor recurrence after radiotherapy, all expressing epidermal growth factor receptor variant III (EGFRvIII), were assessed by a technique that combines fluorescent in situ hybridization (FISH) for the EGFR/CEP7 chromosomal probe with immunostaining for endothelial cells (CD31) and activated pericytes (α Smooth Muscle Actin)...
April 30, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29603739/vascular-targeting-of-light-normalizes-blood-vessels-in-primary-brain-cancer-and-induces-intratumoural-high-endothelial-venules
#9
Bo He, Arnaud Jabouille, Veronica Steri, Anna Johansson-Percival, Iacovos P Michael, Venkata Ramana Kotamraju, Reimar Junckerstorff, Anna K Nowak, Juliana Hamzah, Gabriel Lee, Gabriele Bergers, Ruth Ganss
High-grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed the ability of micelle-tagged, vascular homing peptides RGR, CGKRK and NGR to specifically bind to blood vessels in syngeneic orthotopic GBM models. By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity...
June 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29590646/human-glioblastoma-derived-mesenchymal-stem-cell-to-pericytes-transition-and-angiogenic-capacity-in-glioblastoma-microenvironment
#10
Dongye Yi, Wei Xiang, Qing Zhang, Yongcun Cen, Qing Su, Fangcheng Zhang, Yinping Lu, Hongyang Zhao, Peng Fu
BACKGROUND/AIMS: Tumor vascular formation and maintenance are crucial events in glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to differentiate into pericytes and contribute to neovascularization in the glioma microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb-MSCs), which consist of CD90-MSCs and CD90+MSCs, are a subpopulation of MSCs that are more active in glioma vascularization. However, the functions of gb-MSCs and the microRNA (miRNA) modifications in the glioblastoma microenvironment have not yet been fully elucidated...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29479841/glioblastoma-activated-pericytes-support-tumor-growth-via-immunosuppression
#11
REVIEW
Isadora F G Sena, Ana E Paiva, Pedro H D M Prazeres, Patrick O Azevedo, Luiza Lousado, Sujit K Bhutia, Alla B Salmina, Akiva Mintz, Alexander Birbrair
Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response...
April 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29427211/treatment-with-5-azacitidine-delay-growth-of-glioblastoma-xenografts-a-potential-new-treatment-approach-for-glioblastomas
#12
Tobias Kratzsch, Susanne Antje Kuhn, Andreas Joedicke, Uwe Karsten Hanisch, Peter Vajkoczy, Jens Hoffmann, Iduna Fichtner
PURPOSE: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. The epigenetically active ribonucleoside analog 5-azacitidine is a new therapy option that changes tumor cell chromatin, which is frequently modified by methylation and deacetylation in malignant gliomas. METHODS: In vitro, we analyzed cell viability, cell apoptosis, and migration of human GBM cells. In vivo, we established subcutaneous and intracerebral GBM mouse models originating from U87MG, U373MG, and primary GBM cells as well as one patient-derived xenograft...
May 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29117147/the-na-k-atpase-%C3%AE-subunit-isoforms-expression-in-glioblastoma-multiforme-moonlighting-roles
#13
Deborah Rotoli, Mariana-Mayela Cejas, María-Del-Carmen Maeso, Natalia-Dolores Pérez-Rodríguez, Manuel Morales, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Recent studies point out that gliomas exploit ion channels and transporters, including Na, K-ATPase, to sustain their singular growth and invasion as they invade the brain parenchyma. Moreover, the different isoforms of the β-subunit of Na, K-ATPase have been implicated in regulating cellular dynamics, particularly during cancer progression. The aim of this study was to determine the Na, K-ATPase β subunit isoform subcellular expression patterns in all cell types responsible for microenvironment heterogeneity of GBM using immunohistochemical analysis...
November 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29100012/targeting-glioma-stem-cell-derived-pericytes-disrupts-the-blood-tumor-barrier-and-improves-chemotherapeutic-efficacy
#14
Wenchao Zhou, Cong Chen, Yu Shi, Qiulian Wu, Ryan C Gimple, Xiaoguang Fang, Zhi Huang, Kui Zhai, Susan Q Ke, Yi-Fang Ping, Hua Feng, Jeremy N Rich, Jennifer S Yu, Shideng Bao, Xiu-Wu Bian
The blood-tumor barrier (BTB) is a major obstacle for drug delivery to malignant brain tumors such as glioblastoma (GBM). Disrupting the BTB is therefore highly desirable but complicated by the need to maintain the normal blood-brain barrier (BBB). Here we show that targeting glioma stem cell (GSC)-derived pericytes specifically disrupts the BTB and enhances drug effusion into brain tumors. We found that pericyte coverage of tumor vasculature is inversely correlated with GBM patient survival after chemotherapy...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29016864/loss-of-host-derived-osteopontin-creates-a-glioblastoma-promoting-microenvironment
#15
Frank Szulzewsky, Nina Schwendinger, Dilansu Güneykaya, Patrick J Cimino, Dolores Hambardzumyan, Michael Synowitz, Eric C Holland, Helmut Kettenmann
Background: Microglia and periphery-derived monocytes infiltrate human and mouse glioblastoma and their density is positively correlated with malignancy. Using microarray and RNA sequencing, we have previously shown that glioblastoma-associated microglia/monocytes (GAMs) express osteopontin/SPP1. Methods: We used quantitative reverse transcriptase PCR, immunofluorescence stainings, western blot, and flow cytometry to identify the various sources of osteopontin (OPN) expression in human and mouse glioblastoma...
February 19, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/28978142/glioblastoma-progression-is-assisted-by-induction-of-immunosuppressive-function-of-pericytes-through-interaction-with-tumor-cells
#16
Rut Valdor, David García-Bernal, Carlos Bueno, Mónica Ródenas, José M Moraleda, Fernando Macian, Salvador Martínez
The establishment of immune tolerance during Glioblastoma Multiforme (GBM) progression, is characterized by high levels expression of anti-inflammatory cytokines, which suppress the function of tumor assocciated myeloid cells, and the activation and expansion of tumor antigen specific T cells. However, the mechanisms underlying the failed anti-tumor immune response around the blood vessels during GBM, are poorly understood. The consequences of possible interactions between cancer cells and the perivascular compartment might affect the tumor growth...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28964848/nerve-glial-antigen-ng-2-is-a-crucial-regulator-of-intercellular-adhesion-molecule-icam-1-expression
#17
Beate M Schmitt, Matthias W Laschke, Oliver G Rössler, Wenhui Huang, Anja Scheller, Michael D Menger, Emmanuel Ampofo
The proteoglycan nerve/glial antigen (NG) 2 is expressed on multiple cell types and mediates cell proliferation and migration. However, little is known about its function in gene regulation. In this study, we demonstrate that in pericytes and glioblastoma cells intercellular adhesion molecule (ICAM)-1, an essential protein for leukocyte adhesion and transmigration, underlies a NG2-dependent expression. As shown by flow cytometry, Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR), silencing of NG2 in human placenta-derived pericytes increased the expression of ICAM-1...
January 2018: Biochimica et biophysica acta. Molecular cell research
https://www.readbyqxmd.com/read/28889334/erratum-to-loss-of-pericytes-in-radiation-necrosis-after-glioblastoma-treatments
#18
Soon-Tae Lee, Youngbeom Seo, Ji-Yeon Bae, Kon Chu, Jin Wook Kim, Seung Hong Choi, Tae Min Kim, Il Han Kim, Sung-Hye Park, Chul-Kee Park
No abstract text is available yet for this article.
June 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/28881671/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#19
Liyong Zhang, Yan Wang, Mohammad H Rashid, Min Liu, Kartik Angara, Nahid F Mivechi, Nita J Maihle, Ali S Arbab, Lan Ko
Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 (PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198(+) pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28824376/the-microvascular-gap-junction-channel-a-route-to-deliver-micrornas-for-neurological-disease-treatment
#20
Dominique Thuringer, Eric Solary, Carmen Garrido
Brain microvascular endothelial cells (BMECs) separate the peripheral blood from the brain. These cells, which are surrounded by basal lamina, pericytes and glial cells, are highly interconnected through tight and gap junctions. Their permeability properties restrict the transfer of potentially useful therapeutic agents. In such a hermetic system, the gap junctional exchange of small molecules between cerebral endothelial and non-endothelial cells is crucial for maintaining tissue homeostasis. MicroRNA were shown to cross gap junction channels, thereby modulating gene expression and function of the recipient cell...
2017: Frontiers in Molecular Neuroscience
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