Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C)-stimulated macrophages

Rose, Mélanie; Duhamel, Marie; Aboulouard, Soulaimane; Kobeissy, Firas; Tierny, Dominique; Fournier, Isabelle; Rodet, Franck

doi:10.1038/s41417-020-00286-1

Cited by 9 publications

(5 citation statements)

References 46 publications

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“…We have also identified Raftlin ( rftn1 ) which is involved in the cell entry of poly(I:C), ligand of TLR3 ( 34 ). It could therefore be a target in therapies involving TLRs ( 35 ).…”

Section: Resultsmentioning

confidence: 99%

Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy

et al. 2021

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Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults. The mortality rate is very high despite different treatments. New therapeutic targets are therefore highly needed. Cell-surface proteins represent attractive targets due to their accessibility, their involvement in essential signaling pathways, and their dysregulated expression in cancer. Moreover, they are potential targets for CAR-based immunotherapy or mRNA vaccine strategies. In this context, we investigated the GBM-associated surfaceome by comparing it to astrocytes cell line surfaceome to identify new specific targets for GBM. For this purpose, biotinylation of cell surface proteins has been carried out in GBM and astrocytes cell lines. Biotinylated proteins were purified on streptavidin beads and analyzed by shotgun proteomics. Cell surface proteins were identified with Cell Surface Proteins Atlas (CSPA) and Gene Ontology enrichment. Among all the surface proteins identified in the different cell lines we have confirmed the expression of 66 of these in patient’s glioblastoma using spatial proteomic guided by MALDI-mass spectrometry. Moreover, 87 surface proteins overexpressed or exclusive in GBM cell lines have been identified. Among these, we found 11 specific potential targets for GBM including 5 mutated proteins such as RELL1, CYBA, EGFR, and MHC I proteins. Matching with drugs and clinical trials databases revealed that 7 proteins were druggable and under evaluation, 3 proteins have no known drug interaction yet and none of them are the mutated form of the identified proteins. Taken together, we discovered potential targets for immune therapy strategies in GBM.

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“…We have also identified Raftlin ( rftn1 ) which is involved in the cell entry of poly(I:C), ligand of TLR3 ( 34 ). It could therefore be a target in therapies involving TLRs ( 35 ).…”

Section: Resultsmentioning

confidence: 99%

Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy

et al. 2021

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“…Rat C6 gliomas employ similar immune system evasion strategies as human glioblastoma (Gieryng et al 2017a) and represent a good model of malignant glioma for pharmacological studies (Lee et al 2016;Gieryng et al 2017b). In addition, rat C6 glioma cells have been used for additive effect of pro-protein convertase inhibitor and anti-tumor factors (Rose et al 2021) as well as in the attenuation of protein kinase Cα, extracellular signal-regulated kinase 1/2 signaling, and suppression of matrix metalloproteinase production (Gieryng et al 2017a). Chrysoeriol, one of the common flavonoids from tropical plants, has been shown to have anti-oxidation (Mishra et al 2003;Kim et al 2010), anti-inflammation, anti-microbial (Cha et al 2009) and especially anticancer effects in multiple myeloma (Yang et al 2010), pancreatic cancer (Zhang et al 2018a, b), lung cancer (Wei et al 2019), and breast cancer (Takemura et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Suppression of PI3K/Akt/mTOR pathway in chrysoeriol-induced apoptosis of rat C6 glioma cells

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Limboonreung

Tuchinda

et al. 2021

In Vitro Cell.Dev.Biol.-Animal

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Chrysoeriol, a dietary methoxyflavonoid which is found in tropical medicinal plants, has been shown to have antioxidant, anti-inflammatory, and antineoplastic properties. The present study aimed to investigate the effects of chrysoeriol and its related mechanisms in rat C6 glioma cells. Cell viability in rat C6 glioma cells were measured by MTT assay. The protein expression levels of cleaved caspase-3, caspase-3, pro-apoptotic (Bax), anti-apoptotic protein (Bcl-2), and Annexin V were detected by Western blot analysis and immunocytochemical staining. Results showed that chrysoeriol significantly decreased cell viability and induced apoptosis in rat C6 glioma cells. Chrysoeriol significantly increased the levels of Bax/Bcl-2 ratio and cleaved caspase-3/caspase-3 ratio. Moreover, treatment with chrysoeriol significantly reduced the phosphorylation of PI3K, Akt, and mTOR expression in ratios. These results suggest that chrysoeriol promote apoptosis in rat C6 glioma cells via suppression of the PI3K/Akt/mTOR signaling pathway, thereby demonstrating the potential antineoplastic effects of chrysoeriol on glioma cells.

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“…Proprotein convertases are in the group of proteases that cleave proteins and turn them into their active or inactive form. Several of their substrates are involved in tumorigenesis and immune suppression [ 15 ].…”

Section: Cancer Hallmarks and Pcmentioning

confidence: 99%

What Are the Roles of Proprotein Convertases in the Immune Escape of Tumors?

et al. 2022

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Protein convertases (PCs) play a significant role in post-translational procedures by transforming inactive precursor proteins into their active forms. The role of PCs is crucial for cellular homeostasis because they are involved in cell signaling. They have also been described in many diseases such as Alzheimer’s and cancer. Cancer cells are secretory cells that send signals to the tumor microenvironment (TME), remodeling the surrounding space for their own benefits. One of the most important components of the TME is the immune system of the tumor. In this review, we describe recent discoveries that link PCs to the immune escape of tumors. Among PCs, many findings have determined the role of Furin (PC3) as a paramount enzyme causing the TME to induce tumor immune evasion. The overexpression of various cytokines and proteins, for instance, IL10 and TGF-B, moves the TME towards the presence of Tregs and, consequently, immune tolerance. Furthermore, Furin is implicated in the regulation of macrophage activity that contributes to the increased impairment of DCs (dendritic cells) and T effector cells. Moreover, Furin interferes in the MHC Class_1 proteolytic cleavage in the trans-Golgi network. In tumors, the T cytotoxic lymphocytes (CTLs) response is impeded by the PD1 receptor (PD1-R) located on CTLs and its ligand, PDL1, located on cancer cells. The inhibition of Furin is a subtle means of enhancing the antitumor response by repressing PD-1 expression in tumors or macrophage cells. The impacts of other PCs in tumor immune escape have not yet been clarified to the extent that Furin has. Accordingly, the influence of other types of PCs in tumor immune escape is a promising topic for further consideration.

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Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C)-stimulated macrophages

Cited by 9 publications

References 46 publications

Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy

Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy

Suppression of PI3K/Akt/mTOR pathway in chrysoeriol-induced apoptosis of rat C6 glioma cells

What Are the Roles of Proprotein Convertases in the Immune Escape of Tumors?

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