Variaciones in vitro de la actividad metabólica de los macrófagos frente a células tumorales de cáncer de pulmón y hepatocarcinoma

  1. Castillo, C. A. 1
  2. Gálvez Fernández, S. M. 1
  3. Wong Chero, P. 1
  4. De la Cruz Oré, J. 1
  5. Infante Varillas, S. F. 1
  1. 1 Universidad de Piura
    info

    Universidad de Piura

    Piura, Perú

    ROR https://ror.org/010xy3m51

Journal:
Anales de la Facultad de Medicina

ISSN: 1025-5583,  1609-9419

Year of publication: 2024

Volume: 85

Issue: 2

Pages: 163-170

Type: Article

DIALNET GOOGLE SCHOLAR lock_openDialnet editor

More publications in: Anales de la Facultad de Medicina

Abstract

Introduction. Metabolic activity determines the phenotype of macrophages, which can be oriented towards activation of defense mechanisms or tissue repair (phenotypic plasticity). Objectives. To evaluate the behavior of the main enzymes involved in the metabolic pathways of energy production in macrophages exposed to two tumor environments. Methods. In vitro experimental study that consisted of measuring the enzymatic activity of hexokinase (HQN), lactate dehydrogenase (LDH), isocitrate dehydrogenase (IDH) and glucose-6-phosphate dehydrogenase (G6P) by spectrophotometric absorbance in macrophages exposed to lung cancer and hepatocarcinoma cells. We compared the medians of enzyme activity between the isolated cell lines and their co-cultures (Kruskal-Wallis (H) test) and the medians of enzyme activity between each co-culture (Mann-Whitney U test). Results. The enzymatic activity of LDH was significantly higher in macrophages exposed to the hepatocellular carcinoma line, at 0 (H = 5,96, p = 0,03), 2 (H = 6,49, p = 0,01) and 6 hours (H = 7,20, p = 0,004). On the contrary, the enzymatic activity of IDH and HQN in cocultures was significantly lower compared to monocultures. The G6P had lower activity after 2 hours in macrophage monocultures compared to cocultures in the hepatocellular carcinoma line. The enzymatic activity of LDH, IDH, G6P and HQN in macrophages exposed to lung cancer cells was lower compared to macrophages and tumor cells in monoculture. Conclusion: The interaction between macrophages and tumor cells produces changes in the ways glucose is used.

Bibliographic References

  • Boutilier AJ, Elsawa SF. Macrophage polarization states in the tumor microenvironment. Int J Mol Sci. 2021;22(13):6995. DOI: 10.3390/ijms22136995.
  • De Jesus A, Keyhani-Nejad F, Pusec CM, Goodman L, Geier JA, Stoolman JS. Hexokinase 1 cellular localization regulates the metabolic fate of glucose. Mol Cell. 2022;82(7):1261-1277. DOI: 10.1016/j.molcel.2022.02.028.
  • Ghafouri-Fard S, Abak A, Tavakkoli Avval S, Shoorei H, Taheri M, Samadian M. The impact of non-coding RNAs on macrophage polarization. Biomed Phar-macother. 2021;142(112):11-21. DOI: 10.1016/j.biopha.2021.112112
  • He L, Jhong J-H, Chen Q, Huang K-Y, Strit-tmatter K, Kreuzer J. Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors. Cell Rep. 2021;37(5):33-54. DOI: 10.1016/j.cel-rep.2021.109955.
  • Holt DJ, Chamberlain LM, Grainger DW. Cell–cell signaling in co-cultures of macrophages and fibroblasts. Biomaterials. 2010;31(36): 9382-94. DOI: 10.1016/j.biomaterials.2010.07.101.
  • Jia K-G, Feng G, Tong Y-S, Tao G-Z, Xu L. miR-206 regulates non-small-cell lung cancer cell aerobic glycolysis by targeting hexokinase 2. J Biochem. 2020;167(4):65–70. DOI: 10.1093/jb/mvz099.
  • Kielbassa K, Vegna S, Ramirez C and Akkari L (2019) Understanding the Origin and Diversity of Macro-phages to Tailor Their Targeting in Solid Cancers. Front. Immunol. 2019;10(2215) 10-35. DOI: 10.3389/fimmu.2019.02215.
  • Kim MJ, Lee C-H, Lee Y, Youn H, Kang KW, Kwon J. Glucose-6-phosphatase expression–mediated [18F]FDG efflux in Murine inflammation and cancer models. Mol Imaging Biol. 2019;21(5):917–925. DOI: 10.1007/s11307-019-01316-7.
  • Lazarov T, Juarez-Carreño S, Cox N, Geissmann F. Physiology and diseases of tissue-resident macrophages. Nature. 2023;618(7966):698–707. DOI: 10.1038/s41586-023-06002-x.
  • Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol. 2020;15(1):12–17. DOI: 10.1146/annurev-pathmechdis-012418-012718.
  • Liu Y, Xu R, Gu H, Zhang E, Qu J, Cao W. Metabolic reprogramming in macrophage responses. Biomarker Research. 2021;9(1):13-30. DOI: 10.1186/s40364-020-00251-y.
  • Meiser J, Krämer L, Sapcariu SC, Battello N, Ghelfi J, D’Herouel AF. Pro-inflammatory Macrophages Sustain Pyruvate Oxidation through Pyruvate Dehydrogenase for the Synthesis of Itaconate and to Enable Cytokine Expression. J Biol Chem. 2016;291(8):32–46. DOI: 10.1074/jbc.M115.676817.
  • Myers KV, Amend SR, Pienta KJ. Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment. Molecular Cancer. 2019;18(1):94-108. DOI: 10.1186/s12943-019-1022-2.
  • Park JV, Chandra R, Cai L, Ganguly D, Li H, Toombs JE. Tumor Cells Modulate Macrophage Phenotype in a Novel In Vitro Co-Culture Model of the NSCLC Tumor Microenvironment. J Thorac Oncol. 2022;17(10):78–91. DOI: 10.1016/j.jtho.2022.06.011.
  • Shin J, Park J, Kim S, Lee J, Choi W, Kim H. Strategies for overcoming immune evasion in bladder cancer. Int J Mol Sci. 2024;25(6):31-51. DOI: 10.3390/ijms25063105.
  • Su K, Huang W, Li X, Xu K, Gu T, Liu Y, et al. Evaluation of lactate dehydrogenase and alkaline phosphatase as predictive biomarkers in the prognosis of hepatocellular carcinoma and development of a new nomogram. J Hepatocell Carcinoma. 2023;10(1):69–79. DOI: 10.2147/JHC.S398632.
  • Sun N, Sun S, Gao Y. Utility of isocitrate de-hydrogenase 1 as a serum protein biomarker for the early detection of non-small-cell lung cancer: A multicenter in vitro diagnostic clinical trial. Cancer Sci. 2020;11(17):39-49. DOI: 10.1111/cas.14387.
  • Wang S, Liu G, Li Y, Pan Y. Metabolic reprogramming induces macrophage polarization in the tumor microenvironment. Front Immunol. 2022;(7).13-22. DOI: 10.3389/fimmu.2022.840029.
  • Xie H., Hanai J. I., Ren J. G., Kats L., Burgess K., Bhargava P. (2014). Targeting lactate dehydrogenase-A inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell. Metab. 19 (5), 795–809. DOI:10.1016/j.cmet.2014.03.003.
  • Xie Y, Tang G, Xie P, Zhao X, Chen C, Li X. High CD204+ tumor-associated macrophage density predicts a poor prognosis in patients with clear cell renal cell carcinoma. J Cancer. 2024;15(6):15–22. DOI: 10.7150/jca.91928.
  • Yang Y, Chong Y, Chen M, Dai W, Zhou X, Ji Y. Targeting lactate dehydrogenase a improves radio-therapy efficacy in non-small cell lung cancer: from bedside to bench. J Transl Med .2021; 19(1):170-184. DOI: 10.1186/s12967-021-02825-2.
Data source: Dialnet