Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications
<p>Represents tumorigenic role of inflammatory mediators, TAMs, TANs, and signaling pathways in glioma. Green color indicates activation/release. TAMs: tumor-associated macrophages; TANs: tumor-associated neutrophils; MCP-1,3: monocyte chemoattractant proteins-1,3; CSF-1,2: colony stimulating factors-1,2; GDNF: glial cell-derived neurotrophic factor; IL-1 α, β, -4, -6, -8, -10: interleukins-1 α, β, -4, -6, -8, -10; CXCL-1, -12; chemokine (C-X-C motif) ligand-1, -12; TNF- α: tumor necrosis factor- α; COX-2: cyclooxygenase-2; PGE2: prostaglandin E2; PDGF: platelet-derived growth factor; TGF β: transforming growth factor β; VEGF: vascular endothelial growth factor; MMP-2, 9: matrix metalloproteinases-2, 9; IGFBP1: insulin-like growth factor-binding protein 1; Bmi-1: B-cell specific Moloney murine virus integration site 1; Arg-1: arginase-1; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; JAK/STAT: Janus kinase-signal transducer and activator of transcription; MAPK: Mitogen-activated protein kinase; PI3K/Akt/mTOR: Phosphatidylinositol-3-kinase-mammalian target of rapamycin; TLRs: Toll-like receptors.</p> "> Figure 2
<p>Representation of the key signaling pathways involved in the inflammation-induced glioma genesis. (<b>A</b>) NF-κB pathway; (<b>B</b>) JAK/STAT pathway; (<b>C</b>) MAP Kinase pathway; (<b>D</b>) PI3K/Akt/mTOR pathway; (<b>E</b>) TLRs pathway. NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; JAK/STAT: Janus kinase-signal transducer and activator of transcription; MAPK: Mitogen-activated protein kinase; PI3K/Akt/mTOR: Phosphatidylinositol-3-kinase-mammalian target of rapamycin; TLRs: Toll-like receptors; IL-1β, -4, -6, -13, -22: interleukins-1β, -4, -6, -13, -22; CXCL-12: chemokine (C-X-C motif) ligand-12; TNF- α: tumor necrosis factor- α; COX-2: cyclooxygenase-2; PDGF: platelet-derived growth factor; TGF β: transforming growth factor β; HGF: hepatocyte growth factor; OS: oxidative stress; TROY: tumor necrosis factor receptor superfamily member 19; pSTAT3: phosphorylated signal transducer and activator of transcription 3; GDNF: glial cell-derived neurotrophic factor; Iκβα: inhibitor of kappa B alpha; EGFR: epidermal growth factor receptor; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; VEGF: vascular endothelial growth factor; MMPs: matrix metalloproteinases; Bax/Bcl-2: Bcl-2-associated X <span class="html-italic">protein</span>, B-cell lymphoma 2; AP-1: activator protein-1; IGFs: insulin-like growth factors; LPS: lipopolysaccharide; PI3K: phosphoinositide 3 kinase; Akt: protein kinase B; PDK: 3-phosphoinositide-dependent kinase 1; PIP2/3: phosphatidylinositol-4, 5-bisphosphate/ phosphatidylinositol-3, 4, 5-triphosphate; mTORC1/mTORC2: mechanistic target of rapamycin complex 1 and 2; TSC1/2: tuberous sclerosis complex 1/2; PTEN: phosphatase and tensin homolog: RTK: receptor tyrosine kinase; Rheb: Ras homolog enriched in brain; CD14: cluster of differentiation 14; MD2: myeloid differentiation factor 2; MyD88: myeloid differentiation factor 88; TIRAP: TIR-containing adaptor protein; TRIF: Toll/IL-1R domain-containing adapter inducing interferon-<span class="html-italic">β</span>; TRAF6, -3: TNF receptor-associated factor 6, -3; TRAM: TRIF-related adaptor molecule; RIP1: receptor-interacting protein 1; TAB-1, 2/3: TAK1-binding protein-1, 2/3; TAK1: TGF-β-activated kinase; TRADD: TNF receptor type 1-associated DEATH domain protein; IGF-1: insulin growth factor-1; CREB: cAMP response element binding protein; IRF3: interferon regulatory factor 3.</p> "> Figure 3
<p>Represents the therapeutic benefits of targeting inflammatory mediators, TAMs, TANs, and signaling pathways in glioma. Red color indicates inhibition/blocking and green color shows activation/upregulation. NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; JAK/STAT: Janus kinase-signal transducer and activator of transcription; MAPK: Mitogen-activated protein kinase; PI3K/Akt/mTOR: Phosphatidylinositol-3-kinase-mammalian target of rapamycin; TLRs: Toll-like receptors; TAMs: tumor-associated macrophages; TANs: tumor-associated neutrophils; IL-1β, -6, -8, -10: interleukins-1β, -6, -8, -10; IL-6R: interleukin-6 receptor; TNF- α: tumor necrosis factor- α; MMP-2/9/14: matrix metalloproteinase-2/9/14; PDGFR-α: platelet-derived growth factor receptor-α; COX-2: cyclooxygenase-2; PGE2: prostaglandin E2; PAI-1: plasminogen activator inhibitor-1; VEGF: vascular endothelial growth factor; NSAIDs: non-steroidal anti-inflammatory drugs; CXCR-4: chemokine receptor type 4; STAT 3: signal transducer and activator of transcription 3; CCL2: chemokine ligand 2; MCP-1: monocyte chemoattractant protein 1; CC5R: chemokine receptor type 5; CBDDC-TANs: cell-based drug delivery carrier—tumor-associated neutrophils; PTX: paclitaxel; pSTAT3: phosphorylated signal transducer and activator of transcription 3; Arg-1: arginase-1; CSF: colony stimulating factor; Akt/PKB: protein kinase B; TMZ: temozolomide; iNOS: inducible nitric oxide synthase; NO: nitric oxide; T cell: T lymphocyte; SOCS: suppressors of cytokine signaling; CTLA-4: cytotoxic T lymphocyte associated protein-4; PD-1: programmed cell death protein-1; CD80/86: cluster of differentiation 80/86; ERK 1/2: extracellular signal-regulated kinase 1/2; JNK: c-Jun N-terminal kinase; RAI14: retinoic acid-induced 14 protein; IFN β: interferon β; B cells: B lymphocytes; DCs: dendritic cells; sil-TRADD: silencing TNF receptor type 1-associated DEATH domain protein; sil-TLR4: silencing Toll-like receptor 4.</p> ">
Abstract
:Simple Summary
Abstract
1. Introduction
2. Glioma Microenvironment
3. Molecular Mechanism of Neuroinflammation
4. Tumorigenic Role of Inflammatory Molecules in Glioma
4.1. Role of Tumor-Associated Macrophages (TAMs) in Glioma Growth and Progression
4.2. Relationship between Inflammatory Mediators and TAMs
4.3. Role of Tumor-Associated Neutrophils in Glioma Growth and Progression
5. Signal Transduction Pathways Involved in Glioma Progression
5.1. NF-κB Signaling Pathway
5.2. JAK/STAT Signaling Pathway
5.3. MAP Kinase Signaling Pathway
5.4. PI3K/Akt/mTOR Signaling Pathway
5.5. TLRs Signaling Pathway
5.5.1. TLR Expression in the Brain
5.5.2. Role of TLR Axis in Glioma Development and Associated Neuroinflammation
5.5.3. Canonical (MyD88)-Dependent TLR Signaling Pathway
5.5.4. Non-Canonical (TRIF)-Dependent TLR Signaling Pathway
5.5.5. TLR Expression and Glioma Progression
6. Therapeutic Applications
6.1. Therapeutic Potential of Targeting Glioma-Derived Inflammatory Mediators
6.2. Therapeutic Potential of Targeting TAMs and TANs in Glioma
6.3. Therapeutic Potential of Targeting Signaling Pathways in Glioma
6.3.1. NF-κB Pathway
6.3.2. JAK/STAT Pathway
6.3.3. MAP Kinase Pathway
6.3.4. PI3K/Akt/mTOR Pathway
6.3.5. TLR Pathway
6.4. Therapeutic Potential of Non-Steroidal Anti-Inflammatory Drugs against Glioma Progression
7. Conclusions and Future Possibilities
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Basheer, A.S.; Abas, F.; Othman, I.; Naidu, R. Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications. Cancers 2021, 13, 4226. https://doi.org/10.3390/cancers13164226
Basheer AS, Abas F, Othman I, Naidu R. Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications. Cancers. 2021; 13(16):4226. https://doi.org/10.3390/cancers13164226
Chicago/Turabian StyleBasheer, Abdul Samad, Faridah Abas, Iekhsan Othman, and Rakesh Naidu. 2021. "Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications" Cancers 13, no. 16: 4226. https://doi.org/10.3390/cancers13164226
APA StyleBasheer, A. S., Abas, F., Othman, I., & Naidu, R. (2021). Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications. Cancers, 13(16), 4226. https://doi.org/10.3390/cancers13164226