Treatment of novel IL17A inhibitor in glioblastoma implementing 3rd generation co-culture cell line and patient-derived tumor model

Khan, Shamsuddin Sultan; Asif, Muhammad; Basheer, Mohamed Khadeer Ahamed; Chen, Wei Kang; Al‐Suede, Fouad Saleih R.; Oon, Chern Ein; Tang, Jing; Majid, Aman Shah Abdul; Majid, Amin Malik Shah Abdul

doi:10.1016/j.ejphar.2017.03.031

Cited by 9 publications

(11 citation statements)

References 49 publications

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“…Only LN229 cells showed enrichment of deiminated proteins in IL-17 KEGG pathway, and this was not found in LN18 cells. Regulation of IL-17 via post-translational deimination may be of interest for recent IL-17 inhibitor treatment approaches, which were shown to decrease GBM tumour hypoxia, angiogenesis and tumour growth in animal models [129]. Furthermore, KEGG pathways for bacterial infection were identified to be deiminated in both GBM cell lines (pathogenic E. coli) but more prominently for LN18 cells (E. coli, salmonella and legionellosis).…”

Section: Discussionmentioning

confidence: 99%

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Uysal-Onganer

MacLatchy

Rayan

et al. 2020

IJMS

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Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 and moesin protein levels, as well as on cell invasion. The PAD3 inhibitor was most effective in modulating EVs to anti-oncogenic signatures (reduced miR21 and miR210, and elevated miR126), to reduce cell invasion and to modulate protein expression of pro-GBM proteins in LN229 cells, while the PAD2 and PAD4 inhibitors were more effective in LN18 cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins relating to cancer, metabolism and inflammation differed between the two GBM cell lines. Our findings highlight roles for the different PAD isozymes in the heterogeneity of GBM tumours and the potential for tailored PAD-isozyme specific treatment.

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Section: Discussionmentioning

confidence: 99%

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Uysal-Onganer

MacLatchy

Rayan

et al. 2020

IJMS

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“…Mitochondria act major actions in neuronal ATP metabolism, energy homeostasis, the oxidative stress and apoptosis (Joshi and Bakowska 2012;Keil et al 2011). Regulation of mitochondrial Ca 2+ uptake could counteract HPX-induced mitochondrial membrane depolarization suppression, stimulate recovery of mitochondrial homeostasis, reduce neuronal oxidative injury and apoptosis, and enhance tissue repair and regeneration in the DBTRG neuronal cells (Cheng et al 2017;Khan et al 2017;Deveci et al 2019). It was reported that LEV modulates mitochondrial biogenesis and attenuates mitochondrial dysfunction, apoptosis and cell death in the HPX-induced oxidative stress of H9C2 cardiomyocyte cells (Sun et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam modulates hypoxia-induced inflammation and oxidative stress via inhibition of TRPV1 channel in the DBTRG glioblastoma cell line

Ertilav

2020

Journal of Cellular Neuroscience and Oxidative Stress

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“…Studies focusing on brain tumors are present contradictory findings. IL-17A can promote the migration of U87 MG and U251 human GBM cells 51 , and inhibition of IL-17A can extend the overall survival of patient-derived tumor-bearing immunodeficient mice 54 . However, one study showed that GBM patients who express high levels of IL-17 survive longer than those expressing lower levels 55 .…”

Section: The Protumor Function Of γδ T Cellsmentioning

confidence: 99%

Function of γδ T cells in tumor immunology and their application to cancer therapy

2021

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T cells of the γδ lineage are unconventional T cells with functions not restricted to MHC-mediated antigen presentation. Because of their broad antigen specificity and NK-like cytotoxicity, γδ T-cell importance in tumor immunology has been emphasized. However, some γδ T-cell subsets, especially those expressing IL-17, are immunosuppressive or tumor-promoting cells. Their cytokine profile and cytotoxicity are seemingly determined by cross-talk with microenvironment components, not by the γδTCR chain. Furthermore, much about the TCR antigen of γδ T cells remains unknown compared with the extreme diversity of their TCR chain pairs. Thus, the investigation and application of γδ T cells have been relatively difficult. Nevertheless, γδ T cells remain attractive targets for antitumor therapy because of their independence from MHC molecules. Because tumor cells have the ability to evade the immune system through MHC shedding, heterogeneous antigens, and low antigen spreading, MHC-independent γδ T cells represent good alternative targets for immunotherapy. Therefore, many approaches to using γδ T cells for antitumor therapy have been attempted, including induction of endogenous γδ T cell activation, adoptive transfer of expanded cells ex vivo, and utilization of chimeric antigen receptor (CAR)-T cells. Here, we discuss the function of γδ T cells in tumor immunology and their application to cancer therapy.

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Treatment of novel IL17A inhibitor in glioblastoma implementing 3rd generation co-culture cell line and patient-derived tumor model

Cited by 9 publications

References 49 publications

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Levetiracetam modulates hypoxia-induced inflammation and oxidative stress via inhibition of TRPV1 channel in the DBTRG glioblastoma cell line

Function of γδ T cells in tumor immunology and their application to cancer therapy

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