Interleukin-8 Secreted by Glioblastoma Cells Induces Microvascular Hyperpermeability Through NO Signaling Involving S-Nitrosylation of VE-Cadherin and p120 in Endothelial Cells

Glioblastoma is a highly aggressive brain tumor, characterized by the formation of dysfunctional blood vessels and a permeable endothelial barrier. S-nitrosylation, a posttranslational modification, has been identified as a regulator of endothelial function. In this work we explored whether S-nitrosylation induced by glioblastoma tumors regulates the endothelial function. As proof of concept, we observed that S-nitrosylation is present in the tumoral microenvironment of glioblastoma in two different animal models. Subsequently, we measured S nitrosylation and microvascular permeability in EAhy296 endothelial cells and in cremaster muscle. In vitro, conditioned medium from the human glioblastoma cell line U87 activates eNOS, causes VE-cadherin- S-nitrosylation and induces hyperpermeability. Blocking Interleukin-8 (IL-8) in the conditioned medium inhibited S-nitrosylation of VE-cadherin and hyperpermeability. Recombinant IL-8 increased endothelial permeability by activating eNOS, S-nitrosylation of VE-cadherin and p120, internalization of VE-cadherin and disassembly of adherens junctions. In vivo, IL-8 induced S-nitrosylation of VE-cadherin and p120 and conditioned medium from U87 cells caused hyperpermeability in the mouse cremaster muscle. We conclude that eNOS signaling induced by glioma cells-secreted IL-8 regulates endothelial barrier function in the context of glioblastoma involving S-nitrosylation of VE-cadherin and p120. Our results suggest that inhibiting S-nitrosylati...
Source: Frontiers in Physiology - Category: Physiology Source Type: research

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Contributors : Guan Ying ; Chen Die ; Zhan Yuefu ; Chen JianqiangSeries Type : Expression profiling by high throughput sequencingOrganism : Rattus norvegicusGliomas is the most common and aggressive primary brain tumor. The C6 glioma cell line has been widely used for decades as experimental model system for the study of glioblastoma growth and invasion. Recently, aquaporin-1 (Aqp1) is reported to facilitate cell migration and potentially involved in tumor progression. Here we overexpressed Aqp1 in C6 cells to examine its potential role in glioblastoma. We found overexpression of Aqp1 in C6 cells significantly increased ce...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Rattus norvegicus Source Type: research
Publication date: 17 September 2019Source: Cell Reports, Volume 28, Issue 12Author(s): Erik R. Abels, Sybren L.N. Maas, Lisa Nieland, Zhiyun Wei, Pike See Cheah, Eric Tai, Christy-Joy Kolsteeg, Sophie A. Dusoswa, David T. Ting, Suzanne Hickman, Joseph El Khoury, Anna M. Krichevsky, Marike L.D. Broekman, Xandra O. BreakefieldSummaryGliomas are primary, diffusely infiltrating brain tumors. Microglia are innate immune cells in the CNS and make up a substantial portion of the tumor mass. Glioma cells shape their microenvironment, communicating with and reprogramming surrounding cells, resulting in enhanced angiogenesis, immune...
Source: Cell Reports - Category: Cytology Source Type: research
When glioma results are inconclusive on MRI, clinicians should consider fluoroethyl-tyrosine...Read more on AuntMinnie.comRelated Reading: How cost-effective is intraoperative MRI for gliomas? FET-PET adds 'relevant' info to pediatric cancer cases FLT-PET points toward survival for glioblastoma patients SNMMI: FET-PET could have answers for brainstem glioma SNMMI: FET-PET aids pediatric brain cancer patients
Source: AuntMinnie.com Headlines - Category: Radiology Source Type: news
In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation–dependent and –independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase (IDH1) mutation status. We found that most tran...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: RESEARCH Source Type: research
ily Andrei M. Mikheev Diffuse invasion into adjacent brain matter by glioblastoma (GBM) is largely responsible for their dismal prognosis. Previously, we showed that the TWIST1 (TW) bHLH transcription factor and its regulated gene periostin (POSTN) promote invasive phenotypes of GBM cells. Since TW functional effects are regulated by phosphorylation and dimerization, we investigated how phosphorylation of serine 68 in TW regulates TW dimerization, POSTN expression, and invasion in glioma cells. Compared with wild-type TW, the hypophosphorylation mutant, TW(S68A), impaired TW heterodimerization with the E12 bHLH trans...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Authors: Zeng J, Wu Y, Zhuang S, Qin L, Hua S, Mungur R, Pan J, Zhu Y, Zhan R Abstract Glioblastoma multiforme (GBM) is the most commonly occurring brain cancer, and is characterized by its poor patient outcomes. The present study examined the mRNA expression levels of the transient receptor potential melastatin (TRPM) family in various types of cancer using the ONCOMINE database, along with their corresponding expression profiles in an array of cancer cell lines based on the Cancer Cell Line Encyclopedia (CCLE) datasets. Kaplan‑Meier plotter survival analysis via the Chinese Glioma Genome Atlas (CGGA) database w...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Publication date: Available online 14 September 2019Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Alexandra A.P. Mansur, Anderson J. Caires, Sandhra M. Carvalho, Nadia S.V. Capanema, Isadora C. Carvalho, Herman S. MansurAbstractGlioblastoma (GBM) is the utmost aggressive and lethal primary brain cancer, which has a poor prognosis and remains virtually incurable. Nanomedicine with emerging disruptive nanotechnology alternatives, including designed supramolecular nanohybrids has excellent potential as multimodal tools against cancer by combining nanomaterials, biomacromolecules, and drugs. Thus, we developed and c...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
Management to host conference call today at 8:30 a.m. Eastern SAN DIEGO, Sept. 12, 2019 -- (Healthcare Sales &Marketing Network) -- Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, today announced that the Toca 5 P... Biopharmaceuticals, Oncology Tocagen, glioma, brain cancer, gene therapy
Source: HSMN NewsFeed - Category: Pharmaceuticals Source Type: news
Gliomas account for the majority of primary human brain tumors and remain a challenging neoplasm for cure due to limited therapeutic options. Cell adhesion molecules play pivotal roles in the growth and progre...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
ConclusionsThe present study suggests that overexpression ofCD44 is associated with a poor prognosis for grade II/III glioma patients. Moreover, our findings suggest thatCD44 could serve as a prognostic biomarker in grade II/III glioma patients.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
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