Effects of pharmacological primary cilium disturbance in the context of in vitro 2D and 3D malignant pleura mesothelioma

Jagirdar, Rajesh; Pitaraki, Eleanna; Kotsiou, Ourania S.; Rouka, Erasmia; Sinis, Sotirios I.; Varsamas, Charalampos; Marnas, Periklis; Stergiopoulou, Elpiniki; Giannou, Anastasios D.; Hatzoglou, Chrissi; Gourgoulianis, Konstantinos; Zarogiannis, Sotirios G.

doi:10.1016/j.bbrc.2023.03.011

Cited by 4 publications

(5 citation statements)

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“…On the other hand, cell shape and nucleus morphology reflect complex genomic and gene expression changes in cancer cells that associate with cell motility and mechanical behavior, especially during metastasis and cancer progression [ 30 – 32 ]. PC has a role in cell migration and spherogenesis in MPM and since dimensionality affects cell morphology the differences in BBS gene expression patterns between 2 and 3D cultures could further be explained by such biological phenomena [ 15 ]. Based on the above it would be reasonable to pursue studies that will demonstrate that gene silencing of differentially expressed BBS genes would affect 2D cell migration and 3D spherogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Considering the involvement of PC in cancer signaling pathways such as Extracellular signal-regulated kinase (ERK)/Mitogen‑activated protein kinase (MAPK), Hedgehog (Hh), and Wnt, further investigation is warranted concerning its role and therapeutic potential in MPM [ 37 ]. Also, in a recent study, we showed that mesothelial PC disturbance by AS and LC has effects is many cancers related phenotypes such as cell migration, spheroid formation and invasion, and mesothelial to mesenchymal potential and therefore future studies should focus on the specific role of each differentially expressed BBS gene in these phenotypes [ 15 ]. A limitation of our study was that we did not provide data on BBS proteins expression since technical difficulties in western blots have been reported previously [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…We previously reported in MPM patients that BBS1 gene expression is a favorable prognostic factor [ 14 ]. Lastly, we recently reported that PC drug-induced perturbation affects both mesothelial and mesothelioma cells, reducing cell viability and migration and variably cell adhesion in 2D, while reducing tumor spheroid formation and collagen matrix invasion in 3D cultures [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Changes in expression of mesothelial BBS genes in 2D and 3D after lithium chloride and ammonium sulphate induction of primary cilium disturbance: a pilot study

et al. 2023

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Background Malignant pleural mesothelioma (MPM), a rare and aggressive pleural tumor, has significant histological and molecular heterogeneity. Primary Cilium (PC), an organelle of emerging importance in malignancies, has been scarcely investigated in MPM. A critical molecular complex for the PC function is the BBSome and here we aimed at assessing its expression patterns in ordinary 2D and spheroid 3D cell cultures. Methods A human benign mesothelial cell line (MeT-5A), MPM cell lines (M14K, epithelioid MPM; MSTO, biphasic MPM), and primary MPM cells (pMPM) were used. Primers specific for the human BBS1, 2, 4, 5, 7, 9, 18 transcripts were designed, and quantitative real-time PCR (qRT-PCR) was done with β-actin as the gene of reference. The relative gene expression across 2D and 3D cultures was analyzed by the expression factor (mean of 1/ΔCt values). With the 2–∆∆Ct method the gene expression fold changes were assessed from qRT-PCR data. Molecular changes using the PC-modulating drugs ammonium sulfate (AS) and lithium chloride (LC) were also determined. Results PC was present in all cells used in the study at approximately 15% of the observed area. BBSome transcripts were differentially expressed in different dimensions of cell culture (2D vs. 3D) in all cell lines and pMPM. Treatment with AS and LC affected the expression of the ciliary BBS2 and BBS18 genes in the benign as well as in the MPM cells. Conclusions These data indicate distinct BBSome molecular profiles in human benign and MPM cells cultured in 2D and 3D dimensions and support the notion that PC genes should be investigated as potential MPM therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in expression of mesothelial BBS genes in 2D and 3D after lithium chloride and ammonium sulphate induction of primary cilium disturbance: a pilot study

et al. 2023

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“…1,11 In the PD research field, the use of 3D cell culture models has still been very limited, whereas in the pleural pathophysiology field, it has been increasingly adopted. [12][13][14] However, a significant body of evidence suggests that the combined use of 2D and 3D cell cultures in the study of the biological behavior of cells under the influence of either stressors or testable drugs is far more informative. [15][16][17] The advantages of 3D cell cultures rely on the provision of an in vitro condition closer to the realistic one in terms of cell-cell and cellextracellular matrix interactions.…”

Section: Introductionmentioning

confidence: 99%

“…In the PD research field, the use of 3D cell culture models has still been very limited, whereas in the pleural pathophysiology field, it has been increasingly adopted 12–14 . However, a significant body of evidence suggests that the combined use of 2D and 3D cell cultures in the study of the biological behavior of cells under the influence of either stressors or testable drugs is far more informative 15–17 .…”

Section: Introductionmentioning

confidence: 99%

Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes

Jagirdar,

Pitaraki,

Rouka

et al. 2023

Artificial Organs

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IntroductionPeritoneal dialysis (PD) is a life maintaining treatment in patients with end‐stage renal disease. Its chronic application leads to peritoneal mesothelial layer denudation and fibrotic transformation along with vascular activation of inflammatory pathways. The impact of different PD fluids (PDF) on mesothelial and endothelial cell function and repair mechanisms are not comprehensively described.Materials and MethodsMesothelial (MeT‐5A) and endothelial cells (EA.hy926) were cultured in 1:1 ratio with cell medium and different PDF (icodextrin‐based, amino acid‐based, and glucose‐based). Cell adhesion, cell migration, and cell proliferation in 2D and spheroid formation and collagen gel contraction assays in 3D cell cultures were performed.ResultsCell proliferation and cell‐mediated gel contraction were both significantly decreased in all conditions. 3D spheroid formation was significantly reduced with icodextrin and amino acid PDF, but unchanged with glucose PDF. Adhesion was significantly increased by amino acid PDF in mesothelial cells and decreased by icodextrin and amino acid PDF in endothelial cells. Migration capacity was significantly decreased in mesothelial cells by all three PDF, while endothelial cells remained unaffected.ConclusionsIn 3D phenotypes the effects of PDF are more uniform in both mesothelial and endothelial cells, mitigating spheroid formation and gel contraction. On the contrary, effects on 2D phenotypes are more uniform in the icodextrin and amino acid PDF as opposed to glucose ones and affect mesothelial cells more variably. 2D and 3D comparative assessments of PDF effects on the main peritoneal membrane cell barriers, the mesothelial and endothelial, could provide useful translational information for PD studies.

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Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review

Ebrahimi,

Ak,

Özel

et al. 2024

ACS Pharmacol. Transl. Sci.

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Pleural mesothelioma (PM), a rare malignant tumor explicitly associated with asbestos and erionite exposures, has become a global health problem due to limited treatment options and a poor prognosis, in which the median life expectancy varies depending on the method of treatment. However, the importance of early diagnosis is emphasized, and the practical methods have not matured yet. This study provides a critical overview of PM, addressing various aspects like epidemiology, etiology, diagnosis, treatment options, and the potential use of advanced technologies like microfluidic chip-based models for research and diagnosis. It initially begins with fundamentals of clinical aspects and then discusses the identification of disease-specific biomarkers in patients’ serum or plasma samples, which could potentially be used for early diagnosis. A detailed investigation of the sophisticated preclinical models is highlighted. Recent three-dimensional (3D) model accomplishments, including microarchitecture modeling by transwell coculture, spheroids, organoids, 3D bioprinting constructs, and ex vivo tumor slices, are discussed comprehensively. On-chip models that imitate physiological processes, such as detection chips and therapeutic screening chips, are assessed as potential techniques. The review concludes with a critical and constructive discussion of the growing interest in the topic and its limitations and suggestions.

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Effects of pharmacological primary cilium disturbance in the context of in vitro 2D and 3D malignant pleura mesothelioma

Cited by 4 publications

References 47 publications

Changes in expression of mesothelial BBS genes in 2D and 3D after lithium chloride and ammonium sulphate induction of primary cilium disturbance: a pilot study

Changes in expression of mesothelial BBS genes in 2D and 3D after lithium chloride and ammonium sulphate induction of primary cilium disturbance: a pilot study

Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes

Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review

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