High-pressure oxygen rewires glucose metabolism of patient-derived glioblastoma cells and fuels inflammasome response

Arienti, Chiara; Pignatta, Sara; Zanoni, Michele; Zamagni, Alice; Cortesi, Michela; Sarnelli, Anna; Romeo, Antonino; Arpa, D.; Longobardi, Pasquale; Bartolini, Daniela; Tosatto, Luigino; Naldini, Antonella; Tesei, Anna

doi:10.1016/j.canlet.2021.02.019

Cited by 12 publications

(14 citation statements)

References 41 publications

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“…The OX group comprises three different cycles of oxidative stress conditions: (a) 72 h of hypoxic culturing conditions (37°C, 1% O 2 ) (HYPOX); (b) full cell growth under normoxic conditions (37°C, 21% O 2 ), followed by 1 h of cell exposure to hyperbaric oxygen (37°C, 1.9 ATA HBO) and then 24 h of normoxic culturing conditions (HBO); and (c) a sequential combination of hypoxic culturing conditions (48 hours, 37°C, 1% O 2 ) and cell exposure to hyperbaric oxygen (1 h, 37°C, 1.9 ATA HBO) (HYPOX+HBO). HBO treatment was carried out by a hyperbaric chamber expressly designed for preclinical studies, as previously described [ 20 ]. In particular, the air inside the chamber is replaced with 100% O 2 , and the pressure increased for 15 min until 1.9 ATA are reached and maintained for 1 h. Finally, decompression from 1.9 ATA back to atmospheric pressure is gradually performed over 15 min.…”

Section: Methodsmentioning

confidence: 99%

Pro-inflammatory RNA:DNA Hybrids Are p53 Independently Boosted by Hyperbaric Oxygen: a Subcellular Distribution Analysis by Automated Quantitative Imaging

et al. 2022

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Purpose RNA:DNA hybrids are co-transcriptional products with acknowledged cytoplasmic pro-inflammatory role as activators of the cGAS-STING pathway. We recently proved them also as radiation-induced senescence messages for the abscopal effect mediation, demonstrating the need for a functional p53 for their production and release in A549 and H1299 tumour cells. However, little is known about their role under different stress conditions, especially in cancer cells. Methods In this work, we open the investigation making use of automated quantitative imaging to characterize the hybrid subcellular distribution in HeLa cells grown under different oxygen pressures or exposed to different ionizing radiation doses. After cell imaging by confocal fluorescent microscopy, we apply automated imaging methods developed on purpose to quantify hybrid foci and nuclear cluster intensity, regional and local density and dimension. Results We show that alteration of culture oxygenation increases hybrid cytoplasmic presence, especially when caused by an hyperoxic environment, with evident hybrid gathering at the cell membrane. Ionizing radiations always fail to increase hybrids, in accordance with the absence of functional p53 in HeLa cells. However, dose-dependent effects are still evident and suggest a threshold dose of 7.5 Gy for remarkable hybrid reduction. Conclusion Together with our previous results, these data demonstrate for the first time that different types of stress can increase hybrid production in cancer cells and by at least two different pathways, one p53-dependent triggerable by ionizing radiations and one p53-independent triggerable by oxidative stress. Together, our findings provide a starting point for understanding hybrid role in tumour stress response.

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Section: Methodsmentioning

confidence: 99%

Pro-inflammatory RNA:DNA Hybrids Are p53 Independently Boosted by Hyperbaric Oxygen: a Subcellular Distribution Analysis by Automated Quantitative Imaging

et al. 2022

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“…The effect of HBOT on human glioblastoma (GBM) was investigated, in laboratory, on patient-derived cells and on microglia cell biology (CHME-5). The results obtained from the combination of HBO and RT clearly showed a radiosensitising effect of HBO on GBM cells grown [ 172 ]. Hypofractionated stereotactic radiotherapy (HSRT) after HBO (HBO-RT) appears to be effective for the treatment of recurrent high-grade glioma (rHGG), as pointed out on a cohort of 9 adult rHGG patients.…”

Section: Translational and Potential Applications Of Hbotmentioning

confidence: 99%

A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities

et al. 2021

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Hyperbaric oxygen therapy (HBOT) consists of using of pure oxygen at increased pressure (in general, 2–3 atmospheres) leading to augmented oxygen levels in the blood (Hyperoxemia) and tissue (Hyperoxia). The increased pressure and oxygen bioavailability might be related to a plethora of applications, particularly in hypoxic regions, also exerting antimicrobial, immunomodulatory and angiogenic properties, among others. In this review, we will discuss in detail the physiological relevance of oxygen and the therapeutical basis of HBOT, collecting current indications and underlying mechanisms. Furthermore, potential areas of research will also be examined, including inflammatory and systemic maladies, COVID-19 and cancer. Finally, the adverse effects and contraindications associated with this therapy and future directions of research will be considered. Overall, we encourage further research in this field to extend the possible uses of this procedure. The inclusion of HBOT in future clinical research could be an additional support in the clinical management of multiple pathologies.

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“…Recent reports have indicated that cancer-derived exosomes from prostate and lung cancer as well as glioblastoma cell lines stimulate the production and release of IL-1β in immune and non-immune cells ( 187 – 189 ). In this setting, cancer-derived exosomes may trigger distinct intracellular signaling pathways in receptor cells, culminating in NF-κB activation and the subsequent expression of the IL-1β gene or the activation of inflammasomes through NLRP3 for the cleavage of pro-IL-1β into its active form ( 190 , 191 ).…”

Section: The Systemic Effect Of Tumor Microenvironment-derived Cytokinesmentioning

confidence: 99%

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

et al. 2022

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The tumor microenvironment is a dynamic, complex, and redundant network of interactions between tumor, immune, and stromal cells. In this intricate environment, cells communicate through membrane–membrane, ligand–receptor, exosome, soluble factors, and transporter interactions that govern cell fate. These interactions activate the diverse and superfluous signaling pathways involved in tumor promotion and progression and induce subtle changes in the functional activity of infiltrating immune cells.The immune response participates as a selective pressure in tumor development. In the early stages of tumor development, the immune response exerts anti-tumor activity, whereas during the advanced stages, the tumor establishes mechanisms to evade the immune response, eliciting a chronic inflammation process that shows a pro-tumor effect.The deregulated inflammatory state, in addition to acting locally, also triggers systemic inflammation that has repercussions in various organs and tissues that are distant from the tumor site, causing the emergence of various symptoms designated as paraneoplastic syndromes, which compromise the response to treatment, quality of life, and survival of cancer patients. Considering the tumor–host relationship as an integral and dynamic biological system, the chronic inflammation generated by the tumor is a communication mechanism among tissues and organs that is primarily orchestrated through different signals, such as cytokines, chemokines, growth factors, and exosomes, to provide the tumor with energetic components that allow it to continue proliferating. In this review, we aim to provide a succinct overview of the involvement of cancer-related inflammation at the local and systemic level throughout tumor development and the emergence of some paraneoplastic syndromes and their main clinical manifestations. In addition, the involvement of these signals throughout tumor development will be discussed based on the physiological/biological activities of innate and adaptive immune cells. These cellular interactions require a metabolic reprogramming program for the full activation of the various cells; thus, these requirements and the by-products released into the microenvironment will be considered. In addition, the systemic impact of cancer-related proinflammatory cytokines on the liver—as a critical organ that produces the leading inflammatory markers described to date—will be summarized. Finally, the contribution of cancer-related inflammation to the development of two paraneoplastic syndromes, myelopoiesis and cachexia, will be discussed.

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High-pressure oxygen rewires glucose metabolism of patient-derived glioblastoma cells and fuels inflammasome response

Cited by 12 publications

References 41 publications

Pro-inflammatory RNA:DNA Hybrids Are p53 Independently Boosted by Hyperbaric Oxygen: a Subcellular Distribution Analysis by Automated Quantitative Imaging

Pro-inflammatory RNA:DNA Hybrids Are p53 Independently Boosted by Hyperbaric Oxygen: a Subcellular Distribution Analysis by Automated Quantitative Imaging

A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

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