Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in‐vitro

Jagirdar, Rajesh; Papazoglou, Eleftherios D.; Pitaraki, Eleanna; Kouliou, Olympia; Rouka, Erasmia; Giannakou, Lydia; Giannopoulos, Stefanos; Sinis, Sotirios I.; Hatzoglou, Chrissi; Gourgoulianis, Konstantinos; Zarogiannis, Sotirios G.

doi:10.1111/1440-1681.13446

Cited by 12 publications

(15 citation statements)

References 46 publications

(50 reference statements)

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“…Furthermore, the hydrophobicity of raw carbon nanotubes hampered their dispersion in biological conditions, causing them to clump together in rope-like formations or tangled clumps. These clusters clump together to create discrete multifocal granulomas, which comprise macrophage and fibroblast aggregates [114,115]. Carbon nanotubes were also found in lymph nodes in the mediastinum.…”

Section: Pathogenicity Of Carbon Nanotubesmentioning

confidence: 99%

Causes and Pathogenesis of Malignant Mesothelioma

Gogou¹,

Zarogiannis²,

Siachpazidou³

et al. 2022

Mesothelioma - Diagnostics, Treatment and Basic Research

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Malignant mesothelioma (MM) is a malignancy that arises from the mesothelium, a thin layer of tissue that covers the body’s serous cavities, such as the pleural, peritoneal, pericardial, and tunica vaginalis of the testis. More than 80% of all mesothelioma cases originate from the pleura and approximately 75–80% of patients are males. It is almost always fatal with most of those affected dying within a year of diagnosis. Asbestos exposure is the most common cause of MM, which mostly affects the pleura. Various factors, including other mineral fibers, carbon nanotubes, or genetic mutations, are also suggested to have a role in the development of MM. The involvement of asbestos, other mineral fibers, nanotechnological products, the simian virus SV40, ionizing radiation, genetic factors, and inflammation in the development of MM has been discussed in this chapter. This study focuses on the role of other mineral fibers, such as erionite, fluoroedenite, balangeroite, and carbon nanotubes, as well as genetic mutations in BAP1 and other genes, in the pathogenesis of MM. The etiology of MM is considered to be complex, and greater knowledge of the pathogenetic pathways may lead to the identification of effective and personalized treatment targets.

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Section: Pathogenicity Of Carbon Nanotubesmentioning

confidence: 99%

Causes and Pathogenesis of Malignant Mesothelioma

Gogou¹,

Zarogiannis²,

Siachpazidou³

et al. 2022

Mesothelioma - Diagnostics, Treatment and Basic Research

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“…Blum et al ( 27 ) employed WISP, a deconvolution method, to show that different morphological phenotypes in MM correspond to distinct transcriptome phenotypes. More recently, Jargidar et al ( 28 ) tested epithelioid, biphasic and sarcomatoid MM cell types in vitro and found that fibronectin (FN) and homologous cell-derived extracellular matrix (hcd-ECM) treated substratum differentially affected the above phenotypes; 3D MM spheroid invasion was higher in fibronectin-collagen matrices in the epithelioid and biphasic cells, while 3D cell cultures of epithelioid and sarcomatoid MM cells in fibronectin-collagen showed a higher contractility compared to hcd-ECM-collagen. Collectively, these results support our findings that histological subtypes are remarkably consistent with the MM-derived epithelioid-like, biphasic-like, and sarcomatoid-like tumor cell populations.…”

Section: Discussionmentioning

confidence: 97%

Dissecting and Reconstructing Matrix in Malignant Mesothelioma Through Histocell-Histochemistry Gradients for Clinical Applications

et al. 2022

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BackgroundMalignant pleural mesotheliomas (MM) are known for their heterogenous histology and clinical behavior. MM histology reveals three major tumor cell populations: epithelioid, sarcomatoid, and biphasic. Using a dissecting approach, we showed that histochemical gradients help us better understand tumor heterogeneity and reconsider its histologic classifications. We also showed that this method to characterize MM tumor cell populations provides a better understanding of the underlying mechanisms for invasion and disease progression.MethodsIn a cohort of 87 patients with surgically excised MM, we used hematoxylin and eosin to characterize tumor cell populations and Movat's pentachrome staining to dissect the ECM matrisome. Next, we developed a computerized semi-assisted protocol to quantify and reconstruct the ECM in 3D and examined the clinical association between the matricellular factors and patient outcome.ResultsEpithelioid cells had a higher matrix composition of elastin and fibrin, whereas, in the sarcomatoid type, hyaluronic acid and total collagen were most prevalent. The 3D reconstruction exposed the collagen I and III that form channels surrounding the neoplastic cell blocks. The estimated volume of the two collagen fractions was 14% of the total volume, consistent with the median estimated area of total collagen (12.05 mm2) for epithelioid MM.ConclusionDifferential patterns in matricellular phenotypes in MM could be used in translational studies to improve patient outcome. More importantly, our data raise the possibility that cancer cells can use the matrisome for disease expansion and could be effectively targeted by anti-collagen, anti-elastin, and/or anti-hyaluronic acid therapies.

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“…Also, cell-ECM interactions have been generally recognized as an important mechanism for tumor cell proliferation, migration and invasion. 36 Thus, the components (including fibronectin, thrombospondin and chondroitin sulfate proteoglycans) of the ECM and related genes may be crucial targets for the development and progression of cancers, including MPM. 37 This hypothesis had been demonstrated by previous studies.…”

Section: Discussionmentioning

confidence: 99%

Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

Xie

et al. 2021

IJGM

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Background Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM. Methods Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein–protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers. Results WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of >0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1). Conclusion These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.

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Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in‐vitro

Cited by 12 publications

References 46 publications

Causes and Pathogenesis of Malignant Mesothelioma

Causes and Pathogenesis of Malignant Mesothelioma

Dissecting and Reconstructing Matrix in Malignant Mesothelioma Through Histocell-Histochemistry Gradients for Clinical Applications

Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

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