Dual Effect of Glucocorticoid-Induced Tumor Necrosis Factor–Related Receptor Ligand Carrying Mesenchymal Stromal Cells on Small Cell Lung Cancer: A Preliminary in vitro Study

Köprü, Çağla Zübeyde; Çağnan, Ilgın; Akar, İrem; Esendağlı, Güneş; Korkusuz, Petek; Günel-Özcan, Ayşen

doi:10.1016/j.jcyt.2018.05.002

Cited by 9 publications

(6 citation statements)

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“…34 Moreover, coculturing with GITRL-overexpressing mesenchymal stem cells enhanced the proliferation of NCI-H28 cells. 35 To clarify this emerging role of GITRL, we investigated its effects on macrophages and observed that the up-regulation of this ligand promoted cell proliferation. Our results are consistent with those of previous reports, which described the ability of GITRL to enhance the proliferation of various cell types.…”

Section: Discussionmentioning

confidence: 99%

Biological role of GITR/GITRL in attributes and immune responses of macrophage

Zhuo

Wang

et al. 2019

Journal of Leukocyte Biology

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Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL), a member of the tumor necrosis factor superfamily, is expressed in APCs and acts as a costimulatory molecule in the immune system. Although the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR)/GITRL system has been modulated to promote or decrease T cellrelated responses in multiple diseases, studies in macrophages are limited. To address this issue, we compared the expression of GITRL in various types of macrophages and analyzed whether GITRL can affect the fundamental properties and major functions of these cells. Our results demonstrated that M1 polarized macrophages had the highest GITRL levels. Furthermore, GITRL overexpression skewed macrophage polarization toward the M1 phenotype, accelerating proliferation and migration and regulating phagocytosis and killing function. Moreover, GITRL-silenced cells showed a loss of these functions, further confirming its vital role. We also developed an acute peritonitis mouse model, in which macrophages were driven to differentiate into a proinflammatory phenotype with GITRL up-regulation, triggering a positive feedback loop. Our results provide molecular insight into how the GITR/GITRL system modulates innate immune responses, suggesting that manipulation of the GITR/GITRL system to treat diseases depends not only on T cell regulation but also on macrophage participation.

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Section: Discussionmentioning

confidence: 99%

Biological role of GITR/GITRL in attributes and immune responses of macrophage

Zhuo

Wang

et al. 2019

Journal of Leukocyte Biology

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“…It was reported that SPP1 could not only be used as a prognostic biomarker of lung cancer but also play a role in mediating macrophage polarization and immune escape [ 38 , 39 ]. In small cell lung cancer, TNFRSF18 has been found to bind to its receptor and induce apoptosis [ 40 ]. The complex of dTAT- AGTR2-Ca2 + could inhibit the growth of Lewis lung carcinoma in mice [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Establishment of the prognostic index of lung squamous cell carcinoma based on immunogenomic landscape analysis

Zhang

Yuan

et al. 2020

Cancer Cell Int

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Background The incidence of lung squamous cell carcinoma (LUSC) increased substantially in recent years. Systematical investigation of the immunogenomic pattern is critical to improve the prognosis of LUSC. Methods Based on the TCGA and GEO dataset, we integrated the immune-related genes (IRGs) expression profile and the overall survival (OS) of 502 patients with LUSC. The survival-related and differentially-expressed IRGs in LUSC patients were evaluated by univariate cox regression and LASSO regression analysis. By applying multivariate cox analysis, a new prognostic indicator based on IRGs was established. We also used CIBERSORT algorithms and TIMER database to analyze immune infiltration of LUSC. Both gene set enrichment analysis (GSEA) and principal component analysis (PCA) was carried out for functional annotation. With the assist of computational biology, we also investigated the latent properties and molecular mechanisms of these LUSC-specific IRGs. We analyzed the correlation between immune checkpoints and risk score. Results A novel prognostic model was established based on 11 IRGS, including CXCL5, MMP12, PLAU, ELN, JUN, RNASE7, JAG1, SPP1, AGTR2, FGFR4, and TNFRSF18. This model performed well in the prognostic forecast, and was also related to the infiltration of immune cells. Besides, the high-risk groups and the low-risk groups exhibited distinct layout modes in PCA analysis, and GSEA results showed that different immune status among these groups. Conclusions In summary, our researches screened out clinically significant IRGs and proved the significance of IRG-based, individualized immune-related biomarkers in monitoring, prognosis, and discern of LUSC.

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“…Cells kept for 24 hours with ACPA and normal medium were fixed in 2% glutaraldehyde and processed as previously performed 40 for ultrastructural analysis by TEM (Jeol JEM-1400, Japan) and attached digital camera (Gatan, Germany).…”

Section: Apoptosis Assaysmentioning

confidence: 99%

ACPA decreases non-small cell lung cancer line growth through Akt/PI3K and JNK pathways in vitro

et al. 2021

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Therapeutic agents used for non-small cell lung cancer (NSCLC) have limited curative efficacy and may trigger serious adverse effects. Cannabinoid ligands exert antiproliferative effect and induce apoptosis on numerous epithelial cancers. We confirmed that CB1 receptor (CB1R) is expressed in NSCLC cells in this study. Arachidonoylcyclopropylamide (ACPA) as a synthetic, CB1R-specific ligand decreased proliferation rate in NSCLC cells by WST-1 analysis and real-time proliferation assay (RTCA). The half-maximal inhibitory concentration (IC50) dose of ACPA was calculated as 1.39 × 10−12 M. CB1 antagonist AM281 inhibited the antiproliferative effect of ACPA. Flow cytometry and ultrastructural analyzes revealed significant early and late apoptosis with diminished cell viability. Nano-immunoassay and metabolomics data on activation status of CB1R-mediated pro-apoptotic pathways found that ACPA inhibited Akt/PI3K pathway, glycolysis, TCA cycle, amino acid biosynthesis, and urea cycle and activated JNK pathway. ACPA lost its chemical stability after 24 hours tested by liquid chromatography-mass spectrometry (LC–MS/MS) assay. A novel ACPA-PCL nanoparticle system was developed by nanoprecipitation method and characterized. Sustained release of ACPA-PCL nanoparticles also reduced proliferation of NSCLC cells. Our results demonstrated that low dose ACPA and ACPA-PCL nanoparticle system harbor opportunities to be developed as a novel therapy in NSCLC patients that require further in vivo studies beforehand to validate its anticancer effect.

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Dual Effect of Glucocorticoid-Induced Tumor Necrosis Factor–Related Receptor Ligand Carrying Mesenchymal Stromal Cells on Small Cell Lung Cancer: A Preliminary in vitro Study

Cited by 9 publications

References 50 publications

Biological role of GITR/GITRL in attributes and immune responses of macrophage

Biological role of GITR/GITRL in attributes and immune responses of macrophage

Establishment of the prognostic index of lung squamous cell carcinoma based on immunogenomic landscape analysis

ACPA decreases non-small cell lung cancer line growth through Akt/PI3K and JNK pathways in vitro

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