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https://www.readbyqxmd.com/read/30097696/targeting-pericytes-for-therapeutic-approaches-to-neurological-disorders
#1
REVIEW
Jinping Cheng, Nils Korte, Ross Nortley, Huma Sethi, Yamei Tang, David Attwell
Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood-brain barrier. Pericytes, an under-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood-brain barrier, capillary blood flow and the movement of immune cells into the brain...
August 10, 2018: Acta Neuropathologica
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
#2
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 Hh 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...
July 31, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29987450/ephb4-mediates-resistance-to-antiangiogenic-therapy-in-experimental-glioma
#3
Christian Uhl, Moritz Markel, Thomas Broggini, Melina Nieminen, Irina Kremenetskaia, Peter Vajkoczy, Marcus Czabanka
INTRODUCTION: Alterations in vascular morphogenesis are hallmarks of antiangiogenesis-resistant tumor vessels. Vascular morphogenesis is regulated by ephrinB2-EphB4 system which may induce different biological effects depending on the oncological and molecular contexts. It was the aim of the current study to characterize the influence of EphB4 on tumor microcirculation after antiangiogenic treatment using different SF126 glioma models. MATERIALS AND METHODS: Using an ecotropic transfection system, empty vector (pLXSN) or EphB4 (EphB4OE ) overexpressing Phoenix-ECO cells were coimplanted with SF126 glioma cells subcutaneously (dorsal skinfold chamber, DSC) and orthotopically (cranial window, CW)...
July 10, 2018: Angiogenesis
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/29590646/human-glioblastoma-derived-mesenchymal-stem-cell-to-pericytes-transition-and-angiogenic-capacity-in-glioblastoma-microenvironment
#6
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/29427211/treatment-with-5-azacitidine-delay-growth-of-glioblastoma-xenografts-a-potential-new-treatment-approach-for-glioblastomas
#7
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
#8
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
#9
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/28646266/pericytes-promote-abnormal-tumor-angiogenesis-in-a-rat-rg2-glioma-model
#10
Junji Hosono, Shunichi Morikawa, Taichi Ezaki, Takakazu Kawamata, Yoshikazu Okada
In glioma angiogenesis, tumor vessels cause morphological and functional abnormalities associated with malignancy and tumor progression. We hypothesized that certain structural changes or scantiness of functional pericytes may be involved in the formation of dysfunctional blood vessels in gliomas. In this study, we performed morphological examinations to elucidate the possible involvement of pericytes in brain tumor vessel abnormalities using a rat RG2 glioma model. After implantation of RG2 glioma cells in the syngeneic rat brain, gliomas were formed as early as day 7...
July 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28602979/inhibition-of-cyp4a-by-a-novel-flavonoid-fla-16-prolongs-survival-and-normalizes-tumor-vasculature-in-glioma
#11
Chenlong Wang, Ying Li, Honglei Chen, Jie Zhang, Jing Zhang, Tian Qin, Chenfan Duan, Xuewei Chen, Yanzhuo Liu, Xiaoyang Zhou, Jing Yang
Glioblastomas rapidly become refractory to anti-VEGF therapies. We previously showed that cytochrome P450 (CYP) 4A-derived 20-hydroxyeicosatetraenoic acid (20-HETE) promotes angiogenesis. Here, we tested whether a novel flavonoid (FLA-16) prolongs survival and normalizes tumor vasculature in glioma through CYP4A inhibition. FLA-16 improved survival, reduced tumor burden, and normalized vasculature, accompanied with the decreased secretion of 20-HETE, VEGF and TGF-β in tumor-associated macrophages (TAMs) and endothelial progenitor cells (EPCs) in C6 and U87 gliomas...
August 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28541444/blood-brain-barrier-pericyte-importance-in-malignant-gliomas-what-we-can-learn-from-stroke-and-alzheimer-s-disease
#12
REVIEW
Sadhana Jackson, Ayman ElAli, Daniela Virgintino, Mark R Gilbert
The pericyte, a constitutive component of the central nervous system, is a poorly understood cell type that envelops the endothelial cell with the intended purpose of regulating vascular flow and endothelial cell permeability. Previous studies of pericyte function have been limited to a small number of disease processes such as ischemic stroke and Alzheimer's disease. Recently, publications have postulated a link between glioma stem cell differentiation and pericyte function. These studies suggest that there may be an important interaction of pericytes with tumor cells and other components of the tumor microenvironment in malignant primary glial neoplasms, most notably glioblastoma...
September 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28534507/cecr1-mediated-cross-talk-between-macrophages-and-vascular-mural-cells-promotes-neovascularization-in-malignant-glioma
#13
C Zhu, I Chrifi, D Mustafa, M van der Weiden, P J M Leenen, D J Duncker, J M Kros, C Cheng
Glioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) is highly expressed by M2-like macrophages in GBM where it defines macrophage M2 polarization and contributes to tumor expansion. In this study, the effect of CECR1 in macrophages on tumor angiogenesis was investigated...
September 21, 2017: Oncogene
https://www.readbyqxmd.com/read/28427981/ultrastructure-of-pericystic-or-intracystic-blood-vessels-in-epidermoid-cysts-a-transmission-electron-microscopy-study-laboratory-investigation
#14
Xiao-Hui Ren, Jun Ma, Chun Zeng, Yi-Lin Sun, Song Lin
OBJECTIVES: Recently, we reported a tendency toward spontaneous hemorrhage in both the preoperative and postoperative periods in patients with intracranial epidermoid cyst (EC). According to our experience, this tendency for spontaneous hemorrhage was partly caused by the pathologic blood vessels adjacent to the EC. This study was designed to testify this hypothesis. METHODS: Twenty-three removable pericystic or intracystic blood vessels from 17 patients with EC were collected during surgery and were then examined by transmission electron microscopy...
July 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28362324/ng2-proteoglycan-enhances-brain-tumor-progression-by-promoting-beta-1-integrin-activation-in-both-cis-and-trans-orientations
#15
REVIEW
William B Stallcup
By physically interacting with beta-1 integrins, the NG2 proteoglycan enhances activation of the integrin heterodimers. In glioma cells, co-localization of NG2 and 31 integrin in individual cells (cis interaction) can be demonstrated by immunolabeling, and the NG2-integrin interaction can be confirmed by co-immunoprecipitation. NG2-dependent integrin activation is detected via use of conformationally sensitive monoclonal antibodies that reveal the activated state of the beta-1 subunit in NG2-positive versus NG2-negative cells...
March 31, 2017: Cancers
https://www.readbyqxmd.com/read/27498157/integrins-in-glioblastoma-still-an-attractive-target
#16
REVIEW
Mayra Paolillo, Massimo Serra, Sergio Schinelli
Integrin-mediated signaling pathways have been found to promote the invasiveness and survival of glioma cells by modifying the brain microenvironment to support the formation of the tumoral niche. A variety of cells in the niche express integrin receptors, including tumor-associated macrophages, fibroblasts, endothelial cells and pericytes. In particular, RGD-binding integrins have been demonstrated to have an important role in the epithelial-mesenchymal transition process, considered the first step in the infiltration of tissue by cancer cells and molecular markers of which have been found in glioma cells...
November 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27259253/hmga2-sustains-self-renewal-and-invasiveness-of-glioma-initiating-cells
#17
Xiaoling Zhong, Xuan Liu, Yamu Li, Man Cheng, Wen Wang, Kuan Tian, Lili Mu, Tao Zeng, Ying Liu, Xiaobing Jiang, Luyang Yu, Liang Gao, Yan Zhou
Glioblastoma multiforme (GBM) is the most common type of brain tumors with dismal outcomes. The mesenchymal phenotype is the hallmark of tumor aggressiveness in GBMs. Perivascular smooth muscle cells (pericytes) are essential in homeostasis of normal and glioma tissues. Here we found HMGA2, an architectural transcription factor that promotes mesenchymal phenotypes in a number of solid tumors, is highly expressed in mesenchymal subtype of GBMs and labels both glioma pericytes and glioma-initiating cells (GICs)...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/26951383/decrease-of-vegf-a-in-myeloid-cells-attenuates-glioma-progression-and-prolongs-survival-in-an-experimental-glioma-model
#18
Nadja Osterberg, Napoleone Ferrara, Jean Vacher, Simone Gaedicke, Gabriele Niedermann, Astrid Weyerbrock, Soroush Doostkam, Hans-Eckart Schaefer, Karl H Plate, Marcia Regina Machein
BACKGROUND: Glioblastomas are highly vascularized tumors with a prominent infiltration of macrophages/microglia whose role in promoting glioma growth, invasion, and angiogenesis has not been fully elucidated. METHODS: The contribution of myeloid-derived vascular endothelial growth factor (VEGF) to glioma growth was analyzed in vivo in a syngeneic intracranial GL261 glioma model using a Cre/loxP system to knock out the expression of VEGF-A in CD11b + myeloid cells...
July 2016: Neuro-oncology
https://www.readbyqxmd.com/read/26935297/hemoglobins-hemorphins-and-11p15-5-chromosomal-region-in-cancer-biology-and-%C3%A4-mmunity-with-special-emphasis-for-brain-tumors
#19
REVIEW
Meric Adil Altinoz, Ilhan Elmaci, Bahri Ince, Aysel Ozpinar, Aydin Murat Sav
In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS)...
May 2016: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/26857280/differential-expression-of-pdgfrb-and-egfr-in-microvascular-proliferation-in-glioblastoma
#20
Guiyan Xu, Jian Yi Li
Glioblastoma (GBM) is the highly malignant glioma and exhibits microvascular proliferation. PCR mRNA arrays and immunohistochemical stains on tissue microarray demonstrated that the expression level of PDGFRB in GBM microvascular proliferation was significantly higher than that in GBM tumor cells while the expression level of EGFR was lower in microvascular proliferation than in GBM tumor cells. PDGFRB protein was selectively expressed in pericytes in GBM microvascular proliferation. By analyzing The Cancer Genome Atlas (TCGA) datasets for GBM, it was found that genomic DNA alterations were the main reason for the high expression of EGFR in GBM tumor cells...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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