Volume 52 Issue 1
Jan.  2021
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ZHAO Kun, SHI Rong-chen, MIAO Hong-ming. A Review of the Lipid Metabolism Reprogramming in Tumor Associated Macrophages[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 45-49. doi: 10.12182/20210160202
Citation: ZHAO Kun, SHI Rong-chen, MIAO Hong-ming. A Review of the Lipid Metabolism Reprogramming in Tumor Associated Macrophages[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 45-49. doi: 10.12182/20210160202

A Review of the Lipid Metabolism Reprogramming in Tumor Associated Macrophages

doi: 10.12182/20210160202
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  • Corresponding author: E-mail: hongmingmiao@sina.com
  • Received Date: 2020-11-03
  • Rev Recd Date: 2020-12-10
  • Publish Date: 2021-01-20
  • Tumor associated macrophages (TAMs) are one of the most common types of stromal cells in solid tumors. They are closely related to the immunosuppressive status of tumor microenvironment and potentiate the malignant progress of tumors. Studies have shown that metabolism in tumor associated macrophages has been reprogrammed and involved in the regulation of their own polarization and corresponding functions and phenotypes. Metabolic reprogramming refers to the alteration of key enzymes activity, substrate and its associated metabolites’ concentration in a certain metabolic pathway, which accounts for the disorder of original metabolic states. In this paper, we mainly concentrated on the lipid metabolic reprogramming of TAMs, including triglycerides, fatty acids and their derivatives, cholesterol, phospholipids, and their regulations on tumor progression. However, the metabolism of tumor and tumor microenvironment cells is highly heterogeneous. It is worthy of further exploration on the similarities and differences of lipid metabolism reprogramming between stromal cells and tumor cells, and the mechanism of how reprogramming modulates cell activity. It will be a new strategy for immunotherapy of tumor with metabolic intervention to accurately target the lipid metabolism reprogramming of TAMs, so as to promote the polarization of TAMs to M1 like macrophages, when synthetically considering the diverse types of tumors and different stages of development.
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  • [1]
    VITALE I, MANIC G, COUSSENS L M, et al. Macrophages and metabolism in the tumor microenvironment. Cell Metab,2019,30(1): 36–50. doi: 10.1016/j.cmet.2019.06.001
    MEHLA K, SINGH P K. Metabolic regulation of macrophage polarization in cancer. Trends Cancer,2019,5(12): 822–834. doi: 10.1016/j.trecan.2019.10.007
    RABOLD K, NETEA M G, ADEMA G J, et al. Cellular metabolism of tumor-associated macrophages—functional impact and consequences. FEBS Lett,2017,591(19): 3022–3041. doi: 10.1002/1873-3468.12771
    DENARDO D G, RUFFELL B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol,2019,19(6): 369–382. doi: 10.1038/s41577-019-0127-6
    SHANG S, JI X, ZHANG L, et al. Macrophage ABHD5 suppresses NFkappaB-dependent matrix metalloproteinase expression and cancer metastasis. Cancer Res,2019,79(21): 5513–5526.
    MIAO H, OU J, PENG Y, et al. Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM. Nat Commun, 2016, 7: 11716[2020-11-03]. https://www.nature.com/articles/ncomms11716. doi: 10.1038/ncomms11716.
    XIANG W, SHI R, KANG X, et al. Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression. Nat Commun,2018,9(1): 2574–2586. doi: 10.1038/s41467-018-04999-8
    OU J, MIAO H, MA Y, et al. Loss of ABHD5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition. Cell Rep,2014,9(5): 1798–1811. doi: 10.1016/j.celrep.2014.11.016
    SU P, WANG Q, BI E, et al. Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages. Cancer Res,2020,80(7): 1438–1450. doi: 10.1158/0008-5472.CAN-19-2994
    VATS D, MUKUNDAN L, ODEGAARD J I, et al. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab,2006,4(1): 13–24. doi: 10.1016/j.cmet.2006.05.011
    MARÉCHAL L, LAVIOLETTE M, RODRIGUE-WAY A, et al. The CD36-PPARγ pathway in metabolic disorders. Int J Mol Sci,2018,19(5): 1529–1544. doi: 10.3390/ijms19051529
    WU L, ZHANG X, ZHENG L, et al. RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis. Cancer Immunol Res,2020,8(5): 710–721. doi: 10.1158/2326-6066.CIR-19-0261
    DENG X, ZHANG P, LIANG T, et al. Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARgamma and NF-kappaB pathways. Int J Mol Med,2015,36(2): 449–454. doi: 10.3892/ijmm.2015.2230
    ZHANG Q, WANG H, MAO C, et al. Fatty acid oxidation contributes to IL-1β secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol, 2018, 94: 27-35[2020-11-03]. https://pubmed.ncbi.nlm.nih.gov/29248877/. doi: 10.1016/j.molimm.2017.12.011.
    ZELENAY S, VAN DER VEEN A G, BÖTTCHER J P, et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell,2015,162(6): 1257–1270. doi: 10.1016/j.cell.2015.08.015
    CEN B, LANG J D, DU Y, et al. Prostaglandin E2 induces miR675-5p to promote colorectal tumor metastasis via modulation of p53 expression. Gastroenterology, 2020, 158(4): 971-984.e10[2020-11-03]. https://pubmed.ncbi.nlm.nih.gov/31734182/. doi: 10.1053/j.gastro.2019.11.013.
    WANG D, DUBOIS R N. Role of prostanoids in gastrointestinal cancer. J Clin Invest,2018,128(7): 2732–2742. doi: 10.1172/JCI97953
    FENG M, JIANG W, KIM B Y S, et al. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nature Reviews Cancer,2019,19(10): 568–586. doi: 10.1038/s41568-019-0183-z
    PRIMA V, KALIBEROVA L N, KALIBEROV S, et al. COX2/mPGES1/PGE2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells. Proc Natl Acad Sci U S A,2017,114(5): 1117–1122. doi: 10.1073/pnas.1612920114
    BIANCHINI F, MASSI D, MARCONI C, et al. Expression of cyclo-oxygenase-2 in macrophages associated with cutaneous melanoma at different stages of progression. Prostaglandins Other Lipid Mediat,2007,83(4): 320–328. doi: 10.1016/j.prostaglandins.2007.03.003
    RINGLEB J, STRACK E, ANGIONI C, et al. Apoptotic cancer cells suppress 5-lipoxygenase in tumor-associated macrophages. J Immunol,2018,200(2): 857–868. doi: 10.4049/jimmunol.1700609
    DAURKIN I, ERUSLANOV E, STOFFS T, et al. Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway. Cancer Res,2011,71(20): 6400–6409. doi: 10.1158/0008-5472.CAN-11-1261
    MCKILLOP I H, GIRARDI C A, THOMPSON K J. Role of fatty acid binding proteins (FABPs) in cancer development and progression. Cell Signal, 2019, 62: 109336[2020-11-03]. https://pubmed.ncbi.nlm.nih.gov/31170472/. doi: 10.1016/j.cellsig.2019.06.001.
    ELSHERBINY M E, EMARA M, GODBOUT R. Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma. Prog Lipid Res,2013,52(4): 562–570. doi: 10.1016/j.plipres.2013.08.004
    ZHANG Y, SUN Y, RAO E, et al. Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages. Cancer Res,2014,74(11): 2986–2998. doi: 10.1158/0008-5472.CAN-13-2689
    RAO E, SINGH P, ZHAI X, et al. Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein. Oncotarget,2015,6(10): 7815–7827. doi: 10.18632/oncotarget.3485
    HAO J, YAN F, ZHANG Y, et al. Expression of adipocyte/macrophage fatty acid-binding protein in tumor-associated macrophages promotes breast cancer progression. Cancer Res,2018,78(9): 2343–2355. doi: 10.1158/0008-5472.CAN-17-2465
    VAN DER VORST E P C, THEODOROU K, WU Y, et al. High-density lipoproteins exert pro-inflammatory effects on macrophages via passive cholesterol depletion and PKC-NF-kappaB/STAT1-IRF1 signaling. Cell Metab,2017,25(1): 197–207. doi: 10.1016/j.cmet.2016.10.013
    GOOSSENS P, RODRIGUEZ-VITA J, ETZERODT A, et al. Membrane cholesterol efflux drives tumor-associated macrophage reprogramming and tumor progression. Cell Metab, 2019, 29(6): 1376−1389.e4[2020-11-03]. https://pubmed.ncbi.nlm.nih.gov/30930171/. doi: 10.1016/j.cmet.2019.02.016.
    WANG N, LAN D, CHEN W, et al. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A,2004,101(26): 9774–9779. doi: 10.1073/pnas.0403506101
    SAG D, CEKIC C, WU R, et al. The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity. Nat Commun, 2015, 6: 6354[2020-11-03]. https://www.nature.com/articles/ncomms7354. doi: 10.1038/ncomms7354.
    SHI S Z, LEE E J, LIN Y J, et al. Recruitment of monocytes and epigenetic silencing of intratumoral CYP7B1 primarily contribute to the accumulation of 27-hydroxycholesterol in breast cancer. Am J Cancer Res,2019,9(10): 2194–2208.
    PARK S J, LEE K P, KANG S, et al. Sphingosine 1-phosphate induced anti-atherogenic and atheroprotective M2 macrophage polarization through IL-4. Cell Signal,2014,26(10): 2249–2258. doi: 10.1016/j.cellsig.2014.07.009
    MACIEL E, NEVES B M, MARTINS J, et al. Oxidized phosphatidylserine mitigates LPS-triggered macrophage inflammatory status through modulation of JNK and NF-kB signaling cascades. Cell Signal, 2019, 61: 30-38.
    REINARTZ S, LIEBER S, PESEK J, et al. Cell type-selective pathways and clinical associations of lysophosphatidic acid biosynthesis and signaling in the ovarian cancer microenvironment. Mol Oncol,2019,13(2): 185–201. doi: 10.1002/1878-0261.12396
    BIAN D, SU S, MAHANIVONG C, et al. Lysophosphatidic acid stimulates ovarian cancer cell migration via a Ras-MEK kinase 1 pathway. Cancer Res,2004,64(12): 4209–4217. doi: 10.1158/0008-5472.CAN-04-0060
    HOUBEN A J, MOOLENAAR W H. Autotaxin and LPA receptor signaling in cancer. Cancer Metastasis Rev,2011,30(3/4): 557–565. doi: 10.1007/s10555-011-9319-7
    ZHANG D, SHI R, XIANG W, et al. The Agpat4/LPA axis in colorectal cancer cells regulates antitumor responses via p38/p65 signaling in macrophages. Signal Transduct Target Ther,2020,5(1): 24–36. doi: 10.1038/s41392-020-0117-y
    RABOLD K, ASCHENBRENNER A, THIELE C, et al. Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics. J Immunother Cancer, 2020, 8(2): e000638[2020-11-03]. https://pubmed.ncbi.nlm.nih.gov/32943450/. doi: 10.1136/jitc-2020-000638.
    EMANUELE S, D'ANNEO A, CALVARUSO G, et al. The double-edged sword profile of redox signaling: oxidative events as molecular switches in the balance between cell physiology and cancer. Chem Res Toxicol,2018,31(4): 201–210. doi: 10.1021/acs.chemrestox.7b00311
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