Mechanism of action of lactic acid in tumor microenvironment and related treatment

doi:10.3760/cma.j.cn371439-20220330-00066

Abstract

Abstract:

Lactic acid, a widespread metabolite in the tumor microenvironment, is mainly produced by tumor cells that undergo aerobic glycolysis. Lactic acid is closely related to the occurrence and development of tumor. It not only serves as a substrate to supply energy to tumor cells, but also acts as a signaling molecule to activate multiple pathways to promote invasive and metastasis, angiogenesis and immune escape of tumor cells. In-depth research on the mechanism of action of lactic acid in the occurrence and development of tumor and related therapeutic progress will help to find drug targets for treatment of tumor and improve prognosis of patients.

Key words: Tumor microenvironment, Lactic acid, Neovascularization, pathologic, Tumor escape, Invasion and metastasis

Zhang Zishu, Wu Xinlin. Mechanism of action of lactic acid in tumor microenvironment and related treatment[J]. Journal of International Oncology, 2022, 49(6): 349-352.

References 30

[1]	Martínez-Reyes I, Chandel NS. Cancer metabolism: looking forward[J]. Nat Rev Cancer, 2021, 21(10): 669-680. DOI: 10.1038/s41568-021-00378-6. doi: 10.1038/s41568-021-00378-6 pmid: 34272515
[2]	Vaupel P, Multhoff G. Revisiting the warburg effect: historical dogma versus current understanding[J]. J Physiol, 2021, 599(6): 1745-1757. DOI: 10.1113/JP278810. doi: 10.1113/JP278810
[3]	Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, et al. Cancer metabolism: a therapeutic perspective[J]. Nat Rev Clin Oncol, 2017, 14(1): 11-31. DOI: 10.1038/nrclinonc.2016.60. doi: 10.1038/nrclinonc.2016.60 pmid: 27141887
[4]	Pérez-Escuredo J, Van Hée VF, Sboarina M, et al. Monocarboxy-late transporters in the brain and in cancer[J]. Biochim Biophys Acta, 2016, 1863(10): 2481-2497. DOI: 10.1016/j.bbamcr.2016.03.013. doi: 10.1016/j.bbamcr.2016.03.013 pmid: 26993058
[5]	Payen VL, Mina E, Van Hée VF, et al. Monocarboxylate transpor-ters in cancer[J]. Mol Metab, 2020, 33: 48-66. DOI: 10.1016/j.molmet.2019.07.006. doi: 10.1016/j.molmet.2019.07.006
[6]	Wang N, Jiang X, Zhang S, et al. Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates[J]. Cell, 2021, 184(2): 370-383. e13. DOI: 10.1016/j.cell.2020.11.043. doi: 10.1016/j.cell.2020.11.043 pmid: 33333023
[7]	Faubert B, Li KY, Cai L, et al. Lactate metabolism in human lung tumors[J]. Cell, 2017, 171(2): 358-371. e9. DOI: 10.1016/j.cell.2017.09.019. doi: 10.1016/j.cell.2017.09.019
[8]	Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated macrophages as treatment targets in oncology[J]. Nat Rev Clin Oncol, 2017, 14(7): 399-416. DOI: 10.1038/nrclinonc.2016.217. doi: 10.1038/nrclinonc.2016.217 pmid: 28117416
[9]	Colegio OR, Chu NQ, Szabo AL, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid[J]. Nature, 2014, 513(7519): 559-563. DOI: 10.1038/nature13490. doi: 10.1038/nature13490
[10]	Chen P, Zuo H, Xiong H, et al. Gpr132 sensing of lactate medi-ates tumor-macrophage interplay to promote breast cancer meta-stasis[J]. Proc Natl Acad Sci U S A, 2017, 114(3): 580-585. DOI: 10.1073/pnas.1614035114. doi: 10.1073/pnas.1614035114
[11]	Wei C, Yang C, Wang S, et al. Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis[J]. Mol Cancer, 2019, 18(1): 64. DOI: 10.1186/s12943-019-0976-4. doi: 10.1186/s12943-019-0976-4
[12]	Kalluri R. The biology and function of fibroblasts in cancer[J]. Nat Rev Cancer, 2016, 16(9): 582-598. DOI: 10.1038/nrc.2016.73. doi: 10.1038/nrc.2016.73 pmid: 27550820
[13]	Kogure A, Naito Y, Yamamoto Y, et al. Cancer cells with high-metastatic potential promote a glycolytic shift in activated fibroblasts[J]. PLoS One, 2020, 15(6): e0234613. DOI: 10.1371/journal.pone.0234613. doi: 10.1371/journal.pone.0234613
[14]	Fitzgerald G, Soro-Arnaiz I, De Bock K. The warburg effect in endothelial cells and its potential as an anti-angiogenic target in cancer[J]. Front Cell Dev Biol, 2018, 6: 100. DOI: 10.3389/fcell.2018.00100. doi: 10.3389/fcell.2018.00100 pmid: 30255018
[15]	Sun S, Li H, Chen J, et al. Lactic acid: no longer an inert and end-product of glycolysis[J]. Physiology (Bethesda), 2017, 32(6): 453-463. DOI: 10.1152/physiol.00016.2017. doi: 10.1152/physiol.00016.2017
[16]	Brown TP, Ganapathy V. Lactate/GPR81 signaling and proton motive force in cancer: role in angiogenesis, immune escape, nutrition, and Warburg phenomenon[J]. Pharmacol Ther, 2020, 206: 107451. DOI: 10.1016/j.pharmthera.2019.107451. doi: 10.1016/j.pharmthera.2019.107451
[17]	Deng F, Zhou R, Lin C, et al. Tumor-secreted dickkopf2 accele-rates aerobic glycolysis and promotes angiogenesis in colorectal cancer[J]. Theranostics, 2019, 9(4): 1001-1014. DOI: 10.7150/thno.30056. doi: 10.7150/thno.30056
[18]	Yang J, Jiang Y, He R, et al. DKK2 impairs tumor immunity infiltration and correlates with poor prognosis in pancreatic ductal adenocarcinoma[J]. J Immunol Res, 2019, 2019: 8656282. DOI: 10.1155/2019/8656282. doi: 10.1155/2019/8656282
[19]	Hu J, Wang Z, Chen Z, et al. DKK2 blockage-mediated immunotherapy enhances anti-angiogenic therapy of Kras mutated colorectal cancer[J]. Biomed Pharmacother, 2020, 127: 110229. DOI: 10.1016/j.biopha.2020.110229. doi: 10.1016/j.biopha.2020.110229
[20]	Hayes C, Donohoe CL, Davern M, et al. The oncogenic and clinical implications of lactate induced immunosuppression in the tumour microenvironment[J]. Cancer Lett, 2021, 500: 75-86. DOI: 10.1016/j.canlet.2020.12.021. doi: 10.1016/j.canlet.2020.12.021
[21]	Brand A, Singer K, Koehl GE, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells[J]. Cell Metab, 2016, 24(5): 657-671. DOI: 10.1016/j.cmet.2016.08.011. doi: 10.1016/j.cmet.2016.08.011
[22]	Bae EA, Seo H, Kim IK, et al. Roles of NKT cells in cancer immunotherapy[J]. Arch Pharm Res, 2019, 42(7): 543-548. DOI: 10.1007/s12272-019-01139-8. doi: 10.1007/s12272-019-01139-8
[23]	de la Cruz-López KG, Castro-Muñoz LJ, Reyes-Hernández DO, et al. Lactate in the regulation of tumor microenvironment and therapeutic approaches[J]. Front Oncol, 2019, 9: 1143. DOI: 10.3389/fonc.2019.01143. doi: 10.3389/fonc.2019.01143 pmid: 31737570
[24]	Raychaudhuri D, Bhattacharya R, Sinha BP, et al. Lactate indu-ces pro-tumor reprogramming in intratumoral plasmacytoid dendritic cells[J]. Front Immunol, 2019, 10: 1878. DOI: 10.3389/fimmu.2019.01878. doi: 10.3389/fimmu.2019.01878 pmid: 31440253
[25]	Shaul ME, Fridlender ZG. Tumour-associated neutrophils in patients with cancer[J]. Nat Rev Clin Oncol, 2019, 16(10): 601-620. DOI: 10.1038/s41571-019-0222-4. doi: 10.1038/s41571-019-0222-4
[26]	Wang JX, Choi SYC, Niu X, et al. Lactic acid and an acidic tumor microenvironment suppress anticancer immunity[J]. Int J Mol Sci, 2020, 21(21): 8363. DOI: 10.3390/ijms21218363. doi: 10.3390/ijms21218363
[27]	Abdel-Wahab AF, Mahmoud W, Al-Harizy RM. Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy[J]. Pharmacol Res, 2019, 150: 104511. DOI: 10.1016/j.phrs.2019.104511. doi: 10.1016/j.phrs.2019.104511
[28]	Chen X, Hao B, Li D, et al. Melatonin inhibits lung cancer development by reversing the Warburg effect via stimulating the SIRT3/PDH axis[J]. J Pineal Res, 2021, 71(2): e12755. DOI: 10.1111/jpi.12755. doi: 10.1111/jpi.12755
[29]	Shen S, Yao T, Xu Y, et al. CircECE1 activates energy meta-bolism in osteosarcoma by stabilizing c-Myc[J]. Mol Cancer, 2020, 19(1): 151. DOI: 10.1186/s12943-020-01269-4. doi: 10.1186/s12943-020-01269-4
[30]	Ippolito L, Morandi A, Giannoni E, et al. Lactate: a metabolic driver in the tumour landscape[J]. Trends Biochem Sci, 2019, 44(2): 153-166. DOI: 10.1016/j.tibs.2018.10.011. doi: S0968-0004(18)30227-5 pmid: 30473428