Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA165673 | ENA |
REPOSITORIES: ENA
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Project description:Malignant gliomas are characterized by marked neovascularization and increased tumor cell proliferation. Recently, membrane alanyl-aminopeptidase (CD13/APN) has been identified to play a crucial role in neoangiogenesis. In this study, we show that among various central nervous system tumors, malignant astrocytomas are unique in their high expression levels of functionally active CD13/APN. CD13/APN was found in both tumor cells and tumor vessels of malignant astrocytomas, while in low-grade astrocytomas only endothelial cells of tumor vessels expressed CD13/APN. Inhibitors of the enzymatic activity of CD13/APN significantly reduced the proliferation of U87MG and U138MG malignant glioma cells. Inhibition of CD13/APN mRNA expression by siRNA in glioma cells co-cultured with human umbilical vein endothelial cells (HUVEC) effectively decreased blood vessel formation. Pro-angiogenic factors like bFGF and VEGF induced CD13/APN expression in glioma cells. Treatment of U87MG and U138MG cells with CD13/APN inhibitors resulted in an increased mRNA expression of VEGF and VEGF receptor 2 (VEGF-R2) in these cells. Taken together, these findings provide evidence that CD13/APN promotes tumor cell proliferation and blood vessel formation in malignant astrocytomas. Remarkably, inhibition of CD13/APN induces an angiogenic expression profile via an autocrine feed-back mechanism involving the VEGF/VEGF-R2 system in malignant gliomas. Experimental design includes altogether four samples with two replicate controls (U87_APN_wt_EGFP) and two replicate samples (U87_APN_L243P_EGFP). Replicates are from two independent experiments.
2012-05-27 | E-GEOD-37923 | biostudies-arrayexpress
Project description:Malignant gliomas are characterized by marked neovascularization and increased tumor cell proliferation. Recently, membrane alanyl-aminopeptidase (CD13/APN) has been identified to play a crucial role in neoangiogenesis. In this study, we show that among various central nervous system tumors, malignant astrocytomas are unique in their high expression levels of functionally active CD13/APN. CD13/APN was found in both tumor cells and tumor vessels of malignant astrocytomas, while in low-grade astrocytomas only endothelial cells of tumor vessels expressed CD13/APN. Inhibitors of the enzymatic activity of CD13/APN significantly reduced the proliferation of U87MG and U138MG malignant glioma cells. Inhibition of CD13/APN mRNA expression by siRNA in glioma cells co-cultured with human umbilical vein endothelial cells (HUVEC) effectively decreased blood vessel formation. Pro-angiogenic factors like bFGF and VEGF induced CD13/APN expression in glioma cells. Treatment of U87MG and U138MG cells with CD13/APN inhibitors resulted in an increased mRNA expression of VEGF and VEGF receptor 2 (VEGF-R2) in these cells. Taken together, these findings provide evidence that CD13/APN promotes tumor cell proliferation and blood vessel formation in malignant astrocytomas. Remarkably, inhibition of CD13/APN induces an angiogenic expression profile via an autocrine feed-back mechanism involving the VEGF/VEGF-R2 system in malignant gliomas.
2012-05-28 | GSE37923 | GEO
Project description:The nervous system plays an increasingly appreciated role in the regulation of cancer. In gliomas, neuronal activity drives tumor progression through paracrine signaling factors such as neuroligin-3 and brain-derived neurotrophic factor (BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. The consequent glioma cell membrane depolarization drives tumor proliferation. In the healthy brain, activity-regulated secretion of BDNF promotes adaptive plasticity of synaptic connectivity and strength. Here, we show that malignant synapses exhibit similar plasticity regulated by BDNF. Signaling through the receptor TrkB (tropomyosin receptor kinase B), BDNF promotes AMPA receptor trafficking to the glioma cell membrane, resulting in increased amplitude of glutamate-evoked currents in the malignant cells. This potentiation of malignant synaptic strength shares mechanistic features with synaptic plasticity that contributes to memory and learning in the healthy brain. BDNF-TrkB signaling also regulates the number of neuron-to-glioma synapses. Abrogation of activity-regulated BDNF secretion from the brain microenvironment or loss of TrkB in human glioma cells robustly inhibits tumor progression. Blocking TrkB genetically or pharmacologically abrogates these effects of BDNF on glioma synapses and substantially prolongs survival in xenograft models of pediatric glioblastoma and diffuse intrinsic pontine glioma (DIPG). Taken together, these findings indicate that BDNF-TrkB signaling promotes malignant synaptic plasticity and augments tumor progression.
2023-03-01 | GSE222481 | GEO
Project description:The nervous system plays an increasingly appreciated role in the regulation of cancer. In gliomas, neuronal activity drives tumor progression through paracrine signaling factors such as neuroligin-3 and brain-derived neurotrophic factor (BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. The consequent glioma cell membrane depolarization drives tumor proliferation. In the healthy brain, activity-regulated secretion of BDNF promotes adaptive plasticity of synaptic connectivity and strength. Here, we show that malignant synapses exhibit similar plasticity regulated by BDNF. Signaling through the receptor TrkB (tropomyosin receptor kinase B), BDNF promotes AMPA receptor trafficking to the glioma cell membrane, resulting in increased amplitude of glutamate-evoked currents in the malignant cells. This potentiation of malignant synaptic strength shares mechanistic features with synaptic plasticity that contributes to memory and learning in the healthy brain. BDNF-TrkB signaling also regulates the number of neuron-to-glioma synapses. Abrogation of activity-regulated BDNF secretion from the brain microenvironment or loss of TrkB in human glioma cells robustly inhibits tumor progression. Blocking TrkB genetically or pharmacologically abrogates these effects of BDNF on glioma synapses and substantially prolongs survival in xenograft models of pediatric glioblastoma and diffuse intrinsic pontine glioma (DIPG). Taken together, these findings indicate that BDNF-TrkB signaling promotes malignant synaptic plasticity and augments tumor progression.
2023-09-19 | GSE222560 | GEO
Project description:Malignant gliomas, including glioblastoma (GBM), are uniformly lethal with inferior prognosis and lack of effective treatment. Although the H2AZ2 variant histone is overexpressed in diverse cancer types where it promotes cancer cell proliferation, there are no H2AZ2 inhibitors to-date for clinical intervention. Here, we explored approaches to pharmacologically target the H2AZ2-dependent pathways in GBM.
2023-06-10 | GSE176539 | GEO
Project description:Malignant gliomas, including glioblastoma (GBM), are uniformly lethal with inferior prognosis and lack of effective treatment. Although the H2AZ2 variant histone is overexpressed in diverse cancer types where it promotes cancer cell proliferation, there are no H2AZ2 inhibitors to-date for clinical intervention. Here, we explored approaches to pharmacologically target the H2AZ2-dependent pathways in GBM.
2022-01-15 | GSE189781 | GEO
Project description:Gliomas synaptically integrate into neural circuits. Prior work has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth and gliomas increasing neuronal excitability. In this study we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumor tissue biopsies and cell biology experiments, we found that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumor-infiltrated cortex well beyond the cortical regions normally recruited in the healthy brain. Site-directed biopsies from regions within the tumor that exhibit high functional connectivity between the tumor and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumor cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumor regions compared to tumor regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 through the FDA-approved drug, gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively impacts both patient survival and language task performance. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumor progression and impairs cognition.
2023-01-20 | GSE223065 | GEO
Project description:Extracellular particles (EPs) including extracellular vesicles and exomeres play a significant role in diseases and therapeutic applications. However, the spatiotemporal dynamics of EPs in vivo remains to be elucidated with a suitable method. In this study, we developed a bioluminescence resonance energy transfer (BRET)-based reporter, PalmGRET, to visualize, track and quantify EPs both in vitro and in vivo. To explore the tropism effect of membrane proteins on EPs from lung metastatic hepatocellular carcimoma (HCC), we established PalmGRET in a mouse hepatocellular carcinoma cell line, HCA1, termed HCA1-PalmGRET. EP harvested from HCA1-PalmGRET cells were processed with gel electrophoresis, followed by in-gel digestion and LC-MS/MS analysis. The identified protein list was compared with published lung tropism databases and four membrane proteins were selected for subsequent gene knockdown experiments: solute carrier organic anion transporter family member 2A1 (Slco2a1), alanine aminopeptidase (Anpep/Cd13), chloride intracellular channel 1 (Clic1), and sodium-hydrogen antiporter 3 regulator 1 (Nherf1). Using PalmGRET, we revealed that knockdown of Slco2a1, Cd13 and Clic1 significantly reduced lung tropism of HCC-EPs with varying redirected delivery to other organs.
2021-09-09 | PXD020446 | Pride
Project description:MEOX2 homeobox gene promotes growth of malignant gliomas
| PRJNA750780 | ENA
Project description:Lipidomic analysis of malignant brain gliomas to search for biomarkers.
2020-07-05 | MSV000085693 | GNPS