skip to main content
10.1145/3502871.3502900acmotherconferencesArticle/Chapter ViewAbstractPublication PagesicbbeConference Proceedingsconference-collections
research-article

Investigating The Possible Effect of Gak-3βinhibitor on Macrophage Transformation Via TLR3 and 4 Signaling Pathway

Published: 14 March 2022 Publication History

Abstract

While a great number of immunotherapy strategies are promising in treating many types of cancer via targeting and strengthening adaptive immune responses, finding antitumor strategies through facilitating the innate immune response is still an urgent need in treating broader types of tumor. Previous studies have shown that GSK-3β could affect the expression of toll-like receptors (TLRs) which aids in the transformation of M2 macrophages to M1, slowing the development of cancer tumors. In this study, we analyzed the potential immunotherapy approach for treating glioblastoma, an aggressive brain cancer that is highly refractory to conventional treatment by using GSK-3β inhibitors to manipulate macrophage polarization via TLR-3 and TLR-4. The success of this study could bring up a new target for regulating the tumor progression.

References

[1]
Janeway, Charles A Jr, and Ruslan Medzhitov. “Innate immune recognition.” Annual review of immunology vol. 20 (2002): 197-216.
[2]
Murphy, Kenneth (Kenneth M.), and Casey Weaver. Janeway's Immunobiology / Kenneth Murphy, Casey Weaver ; with Contributions by Allan Mowat, Leslie Berg, David Chaplin ; with Acknowledgment to Charles A. Janeway Jr., Paul Travers, Mark Walport. 9th edition. New York, NY: Garland Science/Taylor & Francis Group, LLC, 2017. Print.
[3]
Kawasaki, Takumi, and Taro Kawai. “Toll-like receptor signaling pathways.” Frontiers in immunology vol. 5 461. 25 Sep. 2014.
[4]
Mantovani, Alberto “Cancer-related inflammation.” Nature vol. 454,7203 (2008): 436-44.
[5]
Kelly, Michael G “TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer.” Cancer research vol. 66,7 (2006): 3859-68.
[6]
Bernsmeier, Christine “Patients with acute-on-chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK.” Gastroenterology vol. 148,3 (2015): 603-615.e14.
[7]
Laskin, Debra L “Macrophages and tissue injury: agents of defense or destruction?.” Annual review of pharmacology and toxicology vol. 51 (2011): 267-88.
[8]
Amann, Lukas, and Marco Prinz. “The origin, fate and function of macrophages in the peripheral nervous system-an update.” International immunology vol. 32,11 (2020): 709-717.
[9]
Vidyarthi, Aurobind “TLR-3 Stimulation Skews M2 Macrophages to M1 Through IFN-αβ Signaling and Restricts Tumor Progression.” Frontiers in immunology vol. 9 1650. 19 Jul. 2018.
[10]
Ding, Dongbing “Identification of mannose receptor and CD163 as novel biomarkers for colorectal cancer.” Cancer biomarkers : section A of Disease markers vol. 21,3 (2018): 689-700.
[11]
Yang, Chaogang “Elevated CD163+/CD68+ Ratio at Tumor Invasive Front is Closely Associated with Aggressive Phenotype and Poor Prognosis in Colorectal Cancer.” International journal of biological sciences vol. 15,5 984-998. 10 Mar. 2019.
[12]
Mantovani, Alberto “The chemokine system in diverse forms of macrophage activation and polarization.” Trends in immunology vol. 25,12 (2004): 677-86.
[13]
Liu, Bo “Polarization of M1 tumor associated macrophage promoted by the activation of TLR3 signal pathway.” Asian Pacific journal of tropical medicine vol. 9,5 (2016): 484-8.
[14]
Rakoff-Nahoum, Seth, and Ruslan Medzhitov. “Toll-like receptors and cancer.” Nature reviews. Cancer vol. 9,1 (2009): 57-63.
[15]
Zhu, Weiwen “Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 33,4 (2019): 5208-5219.
[16]
Marchetti, Alessandra “ERK5/MAPK is activated by TGFbeta in hepatocytes and required for the GSK-3beta-mediated Snail protein stabilization.” Cellular signalling vol. 20,11 (2008): 2113-8.
[17]
Martin, Michael “Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3.” Nature immunology vol. 6,8 (2005): 777-84.
[18]
Fried, Iris “Preliminary results of immune modulating antibody MDV9300 (pidilizumab) treatment in children with diffuse intrinsic pontine glioma.” Journal of neuro-oncology vol. 136,1 (2018): 189-195.
[19]
Weller, Michael “European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas.” The Lancet. Oncology vol. 18,6 (2017): e315-e329.
[20]
Ostrom, Quinn T “The epidemiology of glioma in adults: a "state of the science" review.” Neuro-oncology vol. 16,7 (2014): 896-913.
[21]
Kwiatkowska, Aneta “Strategies in gene therapy for glioblastoma.” Cancers vol. 5,4 1271-305. 23 Oct. 2013.
[22]
Baglietto, Laura “Alcohol consumption and risk of glioblastoma; evidence from the Melbourne Collaborative Cohort Study.” International journal of cancer vol. 128,8 (2011): 1929-34.
[23]
Melin, Beatrice S “Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.” Nature genetics vol. 49,5 (2017): 789-794.
[24]
Heenkenda, Menikae K “Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group.” Thrombosis research vol. 183 (2019): 136-142.
[25]
Müller, Elisabeth “Toll-Like Receptor Ligands and Interferon-γ Synergize for Induction of Antitumor M1 Macrophages.” Frontiers in immunology vol. 8 1383. 26 Oct. 2017.
[26]
Anti-Inducible Nitric Oxide Synthase Antibody.” n.d. Accessed August 3, 2021.
[27]
Wang, Huizhi “IFN-beta production by TLR4-stimulated innate immune cells is negatively regulated by GSK3-beta.” Journal of immunology (Baltimore, Md. : 1950) vol. 181,10 (2008): 6797-802.
[28]
Liu, Jian-Hua “The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3β and MyD88/NF-κB signalling pathways.” Experimental cell research vol. 394,2 (2020): 112157.
[29]
Semenkow, Samantha “An immunocompetent mouse model of human glioblastoma.” Oncotarget vol. 8,37 61072-61082. 15 May. 2017.
[30]
Lee, Su Hyun “Tumor growth rate of invasive breast cancers during wait times for surgery assessed by ultrasonography.” Medicine vol. 95,37 (2016): e4874.
[31]
Kimura, Tetsuya “GSK-3beta is required for memory reconsolidation in adult brain.” PloS one vol. 3,10 (2008): e3540.
[32]
Jost, Sarah C “Measuring brain tumor growth: combined bioluminescence imaging-magnetic resonance imaging strategy.” Molecular imaging vol. 8,5 (2009): 245-53.
[33]
Nelson, Sarah J. “Magnetic resonance spectroscopic imaging. Evaluating responses to therapy for gliomas.” IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society vol. 23,5 (2004): 30-9.
[34]
Li, Yuqian “Data analysis and tissue type assignment for glioblastoma multiforme.” BioMed research international vol. 2014 (2014): 762126.
[35]
Watabe, Tadashi “Theranostics Targeting Fibroblast Activation Protein in the Tumor Stroma: 64Cu- and 225Ac-Labeled FAPI-04 in Pancreatic Cancer Xenograft Mouse Models.” Journal of nuclear medicine : official publication, Society of Nuclear Medicine vol. 61,4 (2020): 563-569.
[36]
Ma, Yunfeng “IL-6, IL-8 and TNF-α levels correlate with disease stage in breast cancer patients.” Advances in clinical and experimental medicine : official organ Wroclaw Medical University vol. 26,3 (2017): 421-426.
[37]
Mills, C D “M-1/M-2 macrophages and the Th1/Th2 paradigm.” Journal of immunology (Baltimore, Md. : 1950) vol. 164,12 (2000): 6166-73.
[38]
Bogdan, C “The role of nitric oxide in innate immunity.” Immunological reviews vol. 173 (2000): 17-26.
[39]
Ugolkov, Andrey “Combination Treatment with the GSK-3 Inhibitor 9-ING-41 and CCNU Cures Orthotopic Chemoresistant Glioblastoma in Patient-Derived Xenograft Models.” Translational oncology vol. 10,4 (2017): 669-678.
[40]
Zhan, Changyou, and Weiyue Lu. “The blood-brain/tumor barriers: challenges and chances for malignant gliomas targeted drug delivery.” Current pharmaceutical biotechnology vol. 13,12 (2012): 2380-7.
[41]
Shabani, Maryam “Resveratrol alleviates obesity-induced skeletal muscle inflammation via decreasing M1 macrophage polarization and increasing the regulatory T cell population.” Scientific reports vol. 10,1 3791. 2 Mar. 2020.
[42]
Valvezan, Alexander J “Adenomatous polyposis coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity.” The Journal of biological chemistry vol. 287,6 (2012): 3823-32.
[43]
Hao, Wenwei “miR-1287-5p upregulation inhibits the EMT and pro-inflammatory cytokines in LPS-induced human nasal epithelial cells (HNECs).” Transplant immunology, vol. 68 101429. 15 Jun. 2021.
[44]
R. Gómez-Sintes, F. Hernández, J. J. Lucas and J. Avila,2011,GSK-3 Mouse Models to Study Neuronal Apoptosis and Neurodegeneration,Front Mol Neurosci,4,45.
[45]
P. Cohen and M. Goedert,2004,GSK3 inhibitors: development and therapeutic potential,Nat Rev Drug Discov,3,479-87.
[46]
M. Pap and G. M. Cooper,1998,Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway,J Biol Chem,273,19929-32.
[47]
S. Wang, L. Ye, M. Li, J. Liu and Y. Sun,2016,GSK-3β Inhibitor CHIR-99021 Promotes Proliferation Through Upregulating β-Catenin in Neonatal Atrial Human Cardiomyocytes,Journal of Cardiovascular Pharmacology,68,425.
[48]
Anand, Prakash, Singh, Prachi, Umbarkar, Yuanjun, Guo, Thomas, Force and Manisha,2018,Inhibition of GSK-3 to induce cardiomyocyte proliferation-a recipe for in situ cardiac regeneration,Cardiovascular research.

Recommendations

Comments

Information & Contributors

Information

Published In

cover image ACM Other conferences
ICBBE '21: Proceedings of the 2021 8th International Conference on Biomedical and Bioinformatics Engineering
November 2021
216 pages
ISBN:9781450385077
DOI:10.1145/3502871
Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

Publisher

Association for Computing Machinery

New York, NY, United States

Publication History

Published: 14 March 2022

Permissions

Request permissions for this article.

Check for updates

Author Tags

  1. Cancer Immunotherapy
  2. Glioblastoma
  3. Macrophage
  4. Toll-like Receptor

Qualifiers

  • Research-article
  • Research
  • Refereed limited

Conference

ICBBE '21

Contributors

Other Metrics

Bibliometrics & Citations

Bibliometrics

Article Metrics

  • 0
    Total Citations
  • 43
    Total Downloads
  • Downloads (Last 12 months)18
  • Downloads (Last 6 weeks)0
Reflects downloads up to 23 Feb 2025

Other Metrics

Citations

View Options

Login options

View options

PDF

View or Download as a PDF file.

PDF

eReader

View online with eReader.

eReader

HTML Format

View this article in HTML Format.

HTML Format

Figures

Tables

Media

Share

Share

Share this Publication link

Share on social media