Cell – extracellular matrix interaction in glioma growth. In silico model

Kalinin, Vladimir I.

doi:10.1515/jib-2020-0027

Cited by 9 publications

(9 citation statements)

References 99 publications

(237 reference statements)

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“…Furthermore, we also noticed a sharp correlation between all miRNAs and fatty acid biosynthesis in these tumors. These results showed that GPX7 -associated miRNAs dysregulated different pathways in gliomas, converging mainly to the regulation of the extracellular matrix, which has a dramatic influence on glioma invasiveness and aggressiveness 91 .…”

Section: Resultsmentioning

confidence: 88%

Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas

Ferreira

Vitiello

Medina

et al. 2022

Sci Rep

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Gliomas are the most commonly occurring malignant brain tumor characterized by an immunosuppressive microenvironment accompanied by profound epigenetic changes, thus influencing the prognosis. Glutathione peroxidase 7 (GPX7) is essential for regulating reactive oxygen species homeostasis under oxidative stress. However, little is known about the function of GPX7 in gliomas. In this study, we hypothesized that GPX7 methylation status could influence biological functions and local immune responses that ultimately impact prognosis in adult gliomas. We conducted an integrated bioinformatics analysis mining GPX7 DNA methylation status, transcriptional and survival data of glioma patients. We discovered that GPX7 was remarkably increased in glioma tissues and cell lines, and was associated with poor prognosis. This upregulation was significantly linked to clinicopathological and molecular features, besides being expressed in a cell cycle-dependent manner. Our results consistently demonstrated that upregulation of GPX7 is tightly modulated by epigenetic processes, which also impacted the overall survival of patients with low-grade gliomas (LGG). Based on the analysis of biological functions, we found that GPX7 might be involved in immune mechanisms involving both innate and adaptive immunity, type I interferon production and regulation of synaptic transmission in LGG, whereas in GBM, it is mainly related to metabolic regulation of mitochondrial dynamics. We also found that GPX7 strongly correlates with immune cell infiltration and diverse immune cell markers, suggesting its role in tumor-specific immune response and in regulating the migration of immune cell types to the tumor microenvironment. Combining these multiple data, we provided the first evidence regarding the epigenetic-mediated regulatory mechanisms underlying GPX7 activation in gliomas. Furthermore, our study brings key insights into the significant effect of GPX7 in modulating both immune molecules and in immune cell infiltration in the microenvironment of gliomas, which might impact the patient outcome, opening up future opportunities to regulate the local immune response.

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Section: Resultsmentioning

confidence: 88%

Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas

Ferreira

Vitiello

Medina

et al. 2022

Sci Rep

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“…GBM shows that there is a robust cell–ECM interaction at play due to extensive ECM compositional alterations, stiffening, and mechanical stresses [ 20 , 98 ]. Here, the process and mechanism of how GBM cells sense this restructures ECM is defined through a couple of mechanosensors and their signaling pathways.…”

Section: Mechanobiology Of Gbm Cells: Adaptive Cellular Signaling Pat...mentioning

confidence: 99%

Physics of Brain Cancer: Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening

et al. 2022

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The biology and physics underlying glioblastoma is not yet completely understood, resulting in the limited efficacy of current clinical therapy. Recent studies have indicated the importance of mechanical stress on the development and malignancy of cancer. Various types of mechanical stress activate adaptive tumor cell responses that include alterations in the extracellular matrix (ECM) which have an impact on tumor malignancy. In this review, we describe and discuss the current knowledge of the effects of ECM alterations and mechanical stress on GBM aggressiveness. Gradual changes in the brain ECM have been connected to the biological and physical alterations of GBM cells. For example, increased expression of several ECM components such as glycosaminoglycans (GAGs), hyaluronic acid (HA), proteoglycans and fibrous proteins result in stiffening of the brain ECM, which alters inter- and intracellular signaling activity. Several mechanosensing signaling pathways have been identified that orchestrate adaptive responses, such as Hippo/YAP, CD44, and actin skeleton signaling, which remodel the cytoskeleton and affect cellular properties such as cell–cell/ECM interactions, growth, and migration/invasion of GBM cells. In vitro, hydrogels are used as a model to mimic the stiffening of the brain ECM and reconstruct its mechanics, which we also discuss. Overall, we provide an overview of the tumor microenvironmental landscape of GBM with a focus on ECM stiffening and its associated adaptive cellular signaling pathways and their possible therapeutic exploitation.

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“…In addition, the movement of the cancer cells is further biased by various adhesionmediated process [54][55][56][57][58][59]. Due to the increasing evidence that gliomas induce a fibrous environment within the brain [72][73][74][75][76][77][78][79][80][81][82], in (1), we model the overall adhesion process using a non-local flux term that was introduced in [26] (see also [19,[27][28][29][30]49,83,84] for similar terms). Specifically, we explore the adhesive interactions of the cancer cells at x ∈ Ω(t) with other neighbouring cancer cells, with the distribution of the non-fibre ECM phase [85][86][87][88] as well as with the oriented fibre ECM phase [89,90], all located within a sensing region B(x, R) of radius R > 0.…”

Section: Cancer Cell Population Dynamicsmentioning

confidence: 99%

Mathematical Modelling of Glioblastomas Invasion within the Brain: A 3D Multi-Scale Moving-Boundary Approach

et al. 2021

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Brain-related experiments are limited by nature, and so biological insights are often limited or absent. This is particularly problematic in the context of brain cancers, which have very poor survival rates. To generate and test new biological hypotheses, researchers have started using mathematical models that can simulate tumour evolution. However, most of these models focus on single-scale 2D cell dynamics, and cannot capture the complex multi-scale tumour invasion patterns in 3D brains. A particular role in these invasion patterns is likely played by the distribution of micro-fibres. To investigate the explicit role of brain micro-fibres in 3D invading tumours, in this study, we extended a previously introduced 2D multi-scale moving-boundary framework to take into account 3D multi-scale tumour dynamics. T1 weighted and DTI scans are used as initial conditions for our model, and to parametrise the diffusion tensor. Numerical results show that including an anisotropic diffusion term may lead in some cases (for specific micro-fibre distributions) to significant changes in tumour morphology, while in other cases, it has no effect. This may be caused by the underlying brain structure and its microscopic fibre representation, which seems to influence cancer-invasion patterns through the underlying cell-adhesion process that overshadows the diffusion process.

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Cell – extracellular matrix interaction in glioma growth. In silico model

Cited by 9 publications

References 99 publications

Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas

Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas

Physics of Brain Cancer: Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening

Mathematical Modelling of Glioblastomas Invasion within the Brain: A 3D Multi-Scale Moving-Boundary Approach

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