GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(5), P. 648 - 664

Published: May 11, 2023

The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications on tumor biology are poorly understood. Here we show that is a prevalent phenomenon glioblastoma (GBM), most frequent and malignant primary brain tumor. We identified horizontal from astrocytes as mechanism enhances tumorigenesis GBM. This dependent network-forming intercellular connections GBM cells astrocytes, which facilitated by growth-associated protein 43 (GAP43), involved neuron axon regeneration astrocyte reactivity. acquisition drives an increase mitochondrial respiration upregulation metabolic pathways linked to proliferation tumorigenicity. Functionally, uptake promotes cycle progression proliferative G2/M phases self-renewal tumorigenicity Collectively, our findings reveal host-tumor interaction cancer cells, providing opportunities for therapeutic development.

Language: Английский

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Mitochondria on the move: Horizontal mitochondrial transfer in disease and health

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(3)

Published: Feb. 16, 2023

Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria shown move between mammalian culture via cytoplasmic bridges. Recent research animals indicates transfer of cancer and during lung injury vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial (HMT) its characteristics consequences been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, trafficking occurs more frequently than previously contributes diverse processes bioenergetic crosstalk homeostasis, disease treatment recovery, development resistance therapy. Here we highlight current knowledge HMT cells, focusing primarily on vivo systems, contend that process is not only (patho)physiologically relevant, but also can exploited the design novel therapeutic approaches.

Language: Английский

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Tumor Microenvironment in Glioma Invasion

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(4), P. 505 - 505

Published: April 15, 2022

A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached distant part. Therefore, complete removal impossible. Recently, research on involvement microenvironment in invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible (HIF) -1α, produced under hypoxia, promotes various related molecules. extracellular matrix surrounding tumors degraded by proteases secreted and simultaneously replaced that infiltration. Astrocytes microglia become tumor-associated astrocytes glioma-associated macrophages/microglia, respectively, relation to cells. These also promote invasion. Interactions between actively each other. Surgery, chemotherapy, radiation therapy transform microenvironment, allowing invade. findings indicate may be a target for On other hand, because living body response tumor, it necessary reconsider whether itself friend or foe brain.

Language: Английский

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Intercellular mitochondrial transfer in the brain, a new perspective for targeted treatment of central nervous system diseases

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(11), P. 3121 - 3135

Published: July 9, 2023

Mitochondria is one of the important organelles involved in cell energy metabolism and regulation also play a key regulatory role abnormal processes such as stress, damage, canceration. Recent studies have shown that mitochondria can be transferred between cells different ways participate occurrence development many central nervous system diseases. We aim to review mechanism mitochondrial transfer progress diseases possibility targeted therapy.The PubMed databank, China National Knowledge Infrastructure Wanfang Data were searched identify experiments intracellular transferrin system. The focus on donors, receptors, pathways, drugs transfer.In system, neurons, glial cells, immune tumor each other. Meanwhile, there are types transfer, including tunneling nanotubes, extracellular vesicles, receptor endocytosis, gap junction channels, intercellular contact. A variety stress signals, release damaged mitochondria, DNA, or other products elevation reactive oxygen species, trigger from donor recipient cells. Concurrently, molecular pathways related inhibitors affect transfer.This study reviews phenomenon summarizes corresponding pathways. Finally, we propose treatment methods may used regulate for

Language: Английский

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Mitochondrial transfer in tunneling nanotubes—a new target for cancer therapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: May 21, 2024

A century ago, the Warburg effect was first proposed, revealing that cancer cells predominantly rely on glycolysis during process of tumorigenesis, even in presence abundant oxygen, shifting main pathway energy metabolism from tricarboxylic acid cycle to aerobic glycolysis. Recent studies have unveiled dynamic transfer mitochondria within tumor microenvironment, not only between but also and stromal cells, immune others. In this review, we explore pathways mechanisms mitochondrial as well how these activities promote aggressiveness, chemotherapy resistance, evasion. Further, discuss research progress potential clinical significance targeting phenomena. We highlight therapeutic intercellular a future anti-cancer strategy enhancing cell-mediated immunotherapy.

Language: Английский

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The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 669 - 669

Published: Jan. 14, 2025

Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive metabolic reprogramming that drives growth and therapeutic resistance. Key pathways, including glycolysis, lactate production, lipid metabolism, are upregulated to sustain survival in the hypoxic nutrient-deprived microenvironment (TME), while glutamine tryptophan metabolism further contribute phenotype of GBM. These alterations impair immune cell function, leading exhaustion stress CD8+ CD4+ T cells favoring immunosuppressive populations such as regulatory (Tregs) M2-like macrophages. Recent studies emphasize role slow-cycling GBM (SCCs), lipid-laden macrophages, tumor-associated astrocytes (TAAs) reshaping GBM’s landscape reinforcing evasion. Genetic mutations, Isocitrate Dehydrogenase (IDH) Epidermal Growth Factor Receptor (EGFR) amplification, Phosphotase Tensin Homolog (PTEN) loss, drive offer potential targets for therapy. Understanding relationship between suppression critical overcoming This review focuses on rewiring GBM, its impact microenvironment, combining targeting with immunotherapy improve clinical outcomes patients.

Language: Английский

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COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 4, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 considered an airway/multi-systemic disease, and demise has been associated with uncontrolled immune response cytokine storm in to the virus. However, lung pathology, response, tissue damage are poorly described understood due safety concerns. Using post-mortem tissues from uninfected deadly cases as well unbiased combined analysis of histology, multi-viral host markers staining, correlative microscopy, confocal, image analysis, we identified three distinct phenotypes COVID-19-induced damage. First, hemorrhage characterized by minimal infiltration large thrombus; Second, excessive cell but no hemorrhagic events. The third phenotype correspond combination two previous ones. We observed loss alveolar wall integrity, detachment pieces, fibroblast proliferation, extensive fibrosis all phenotypes. Although studied were lethal COVID-19, strong was analyzed significant B poor T infiltrations, suggesting exhausted or compromised cellular these patients. Overall, our data show that SARS-CoV-2-induced highly heterogeneous. These individual differences need be understand long-term consequences.

Language: Английский

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Intercellular Communication in the Brain through Tunneling Nanotubes

Cancers, Journal Year: 2022, Volume and Issue: 14(5), P. 1207 - 1207

Published: Feb. 25, 2022

Intercellular communication is essential for tissue homeostasis and function. Understanding how cells interact with each other paramount, as crosstalk between often dysregulated in diseases can contribute to their progression. Cells communicate through several modalities, including paracrine secretion specialized structures ensuring physical contact them. Among these intercellular structures, tunneling nanotubes (TNTs) are now recognized a means of cell-to-cell the exchange cellular cargo, controlled by variety biological triggers, described here. fundamental brain It allows dialogue many cells, neurons, astrocytes, oligodendrocytes, glial microglia, necessary proper development function brain. We highlight here role TNTs connecting physiological functioning pathologies such stroke, neurodegenerative diseases, gliomas. processes could pave way future therapies.

Language: Английский

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Mitochondria Transfer in Brain Injury and Disease

Cells, Journal Year: 2022, Volume and Issue: 11(22), P. 3603 - 3603

Published: Nov. 14, 2022

Intercellular mitochondria transfer is a novel form of cell signalling in which whole are transferred between cells order to enhance cellular functions or aid the degradation dysfunctional mitochondria. Recent studies have observed intercellular glia and neurons brain, mitochondrial has emerged as key neuroprotective mechanism range neurological conditions. In particular, artificial sparked widespread interest potential therapeutic strategy for brain disorders. this review, we discuss mechanisms effects brain. The role conditions, including neurodegenerative disease, injury, neurodevelopmental disorders, discussed well strategies targeting

Language: Английский

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Mitochondrial DNA-targeted therapy: A novel approach to combat cancer

Cell Insight, Journal Year: 2023, Volume and Issue: 2(4), P. 100113 - 100113

Published: July 22, 2023

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that are essential for mitochondrial function cellular homeostasis, participates in important processes of bioenergetics metabolism. Alterations mtDNA associated with various diseases, especially cancers, considered as biomarkers some types tumors. Moreover, alterations have been found to affect the proliferation, progression metastasis cancer cells, well their interactions immune system tumor microenvironment (TME). The role development makes it a significant target treatment. In recent years, many novel therapeutic methods targeting emerged. this study, we first discussed how cancerogenesis is triggered by mutations, including gene copy number, aberrant expression epigenetic modifications. Then, described detail mechanisms underlying between extramitochondrial environment, which crucial understanding efficacy safety mtDNA-targeted therapy. Next, provided comprehensive overview progress therapy strategies mtDNA. We classified them into two categories based on action: indirect direct strategies. Indirect aimed induce damage dysfunction modulating pathways involved stability integrity, while utilized molecules can selectively bind or cleave achieve efficacy. This study highlights importance treatment, will provide insights future research targeted drugs

Language: Английский

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