Keywords
Abstract
The review presents data from modern medical experimental studies on the state of immune cells of the mammary gland with obese and the possibility of the occurrence of tumors.
References
Van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000;152(6). doi:10.1093/aje/152.6.514.
Lahmann PH, Hoffmann K, Allen N, van Gils CH, Khaw KT, Tehard B et al. Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer. 2004;111(5). doi:10.1002/ijc.20315.
White AJ, Nichols HB, Bradshaw PT, Sandler DP. Overall and central adiposity and breast cancer risk in the Sister Study. Cancer. 2015;121(20). doi:10.1002/cncr.29552.
Sebastiani F, Cortesi L, Sant M, Lucarini V, Cirilli C, De Matteis E et al. Increased incidence of breast cancer in postmenopausal women with high body mass index at the Modena Screening Program. J Breast Cancer. 2016;19(3). doi:10.4048/jbc.2016.19.3.283.
Neuhouser ML, Aragaki AK, Prentice RL, Manson JE, Chlebowski R, Carty CL et al. Overweight, obesity, and postmenopausal invasive breast cancer risk: a secondary analysis of the Women’s Health Initiative Randomized Clinical Trials. JAMA Oncol. 2015. doi:2319235 [pii];10.1001/ jamaoncol.2015.1546 [doi].
Suzuki R, Orsini N, Saji S, Key TJ, Wolk A. Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status--a meta-analysis. Int J Cancer. 2009;124(3). doi:10.1002/ijc.23943.
Chen L, Cook LS, Tang MT, Porter PL, Hill DA, Wiggins CL et al. Body mass index and risk of luminal, HER2-overexpressing, and triple negative breast cancer. Breast Cancer Res Treat. 2016;157(3). doi:10.1007/s10549-016-3825-9.
Ritte R, Lukanova A, Berrino F, Dossus L, Tj0nneland A, Olsen A et al. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res. 2012;14(3). doi:10.1186/bcr3186.
Phipps AI, Chlebowski RT, Prentice R, McTiernan A, Stefanick ML, Wactawski-Wende J et al. Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(3). doi:10.1158/1055-9965.EPI-10-0974.
Barrett P, Mercer JG, Morgan PJ. Preclinical models for obesity research. Dis Model Mech. 2016;9(11):1245-55. doi:10.1242/dmm.026443. [PubMed: 27821603]
Coleman DL. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia. 1978;14(3):141-8. [PubMed: 350680]
Ingalls AM, Dickie MM, Snell GD. Obese, a new mutation in the house mouse. J Hered. 1950;41(12):317-8. doi:10.1093/oxfordjournals.jhered.a106073. [PubMed: 14824537]
Collins S, Martin TL, Surwit RS, Robidoux J. Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics. Physiol Behav. 2004;81(2):243-8. doi:10.1016/j.physbeh.2004.02.006. [PubMed: 15159170]
West DB, Boozer CN, Moody DL, Atkinson RL. Dietary obesity in nine inbred mouse strains. Am J Physiol. 1992;262(6 Pt 2):R1025-32. doi:10.1152/ajpregu.1992.262.6.R1025. [PubMed: 1621856]
Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet-induced type II diabetes in C57BL/6J mice. Diabetes. 1988;37(9):1163-7. doi:10.2337/diab.37.9.1163. [PubMed: 3044882]
Montgomery MK, Hallahan NL, Brown SH, Liu M, Mitchell TW, Cooney GJ et al. Mouse strain- dependent variation in obesity and glucose homeostasis in response to high-fat feeding. Diabetologia. 2013;56(5):1129-39. doi:10.1007/s00125-013-2846-8 [doi]. [PubMed: 23423668]
Olson LK, Tan Y, Zhao Y, Aupperlee MD, Haslam SZ. Pubertal exposure to high fat diet causes mouse strain-dependent alterations in mammary gland development and estrogen responsiveness. Int J Obes. 2010;34(9):1415-26. doi:10.1038/ijo.2010.51.
Panchal SK, Brown L. Rodent models for metabolic syndrome research. J Biomed Biotechnol. 2011;2011:351982. doi:10.1155/2011/351982. [PubMed: 21253582]
Lutz TA, Woods SC. Overview of animal models of obesity. Curr Protoc Pharmacol. 2012;Chapter 5:Unit5.61. doi:10.1002/0471141755.ph0561s58.
Giles ED, Jackman MR, MacLean PS. Modeling diet-induced obesity with obesity-prone rats: implications for studies in females. Front Nutr. 2016;3:50. doi:10.3389/fnut.2016.00050.
Imaoka T, Nishimura M, Daino K, Morioka T, Nishimura Y, Uemura H et al. A rat model to study the effects of diet-induced obesity on radiation-induced mammary carcinogenesis. Radiat Res. 2016;185(5):505-15. doi:10.1667/rr14309.1. [PubMed: 27135968]
Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K et al. A lineage of myeloid cells independent of myb and hematopoietic stem cells. Science. 2012;336(6077). doi:10.1126/science.1219179.
Hassnain Waqas SF, Noble A, Hoang AC, Ampem G, Popp M, StrauB S et al. Adipose tissue macrophages develop from bone marrow-independent progenitors in Xenopus laevis and mouse. J Leukoc Biol. 2017;102(3). doi:10.1189/jlb.1A0317-082RR.
Jappinen N, Felix I, Lokka E, Tyystjarvi S, Pynttari A, Lahtela T et al. Fetal-derived macrophages dominate in adult mammary glands. Nature Commun. 2019;10(1):281. doi:10.1038/ s41467-018-08065-1. [PubMed: 30655530]
Russo L, Lumeng CN. Properties and functions of adipose tissue macrophages in obesity. Immunol. 2018;155(4):407-17. doi:10.1111/imm.13002.
Stewart TA, Hughes K, Hume DA, Davis FM. Developmental stage-specific distribution of macrophages in mouse mammary gland. Front Cell Dev Biol. 2019;7:250. doi:10.3389/ fcell.2019.00250. [PubMed: 31709255]
Gyorki DE, Asselin-Labat ML, van Rooijen N, Lindeman GJ, Visvader JE. Resident macrophages influence stem cell activity in the mammary gland. Breast Cancer Res. 2009;11(4):R62. doi:10.1186/bcr2353. [PubMed: 19706193]
Chakrabarti R, Celia-Terrassa T, Kumar S, Hang X, Wei Y, Choudhury A et al. Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche. Science. 2018;360(6396). doi:10.1126/science.aan4153.
O’Brien J, Lyons T, Monks J, Lucia MS, Wilson RS, Hines L et al. Alternatively activated macrophages and collagen remodeling characterize the postpartum involuting mammary gland across species. Am J Pathol. 2010;176(3):1241-55. doi:10.2353/ajpath.2010.090735. [PubMed: 20110414]
Muir LA, Kiridena S, Griffin C, DelProposto JB, Geletka L, Martinez-Santibanez G et al. Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages. J Leukoc Biol. 2018;103(4):615-28. doi:10.1002/jlb.3hi1017-422r. [PubMed: 29493813]
Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006;116(6):1494-505. doi:10.1172/JCI26498. [PubMed: 16691291]
Oh DY, Morinaga H, Talukdar S, Bae EJ, Olefsky JM. Increased macrophage migration into adipose tissue in obese mice. Diabetes. 2012;61(2):346-54. doi:10.2337/db11-0860. [PubMed: 22190646]
Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes. 2007;56(1):16-23. doi:10.2337/db06-1076. [PubMed: 17192460]
Kaplan JL, Marshall MA, C CM, Harmon DB, Garmey JC, Oldham SN et al. Adipocyte progenitor cells initiate monocyte chemoattractant protein-1-mediated macrophage accumulation in visceral adipose tissue. Mol Metab. 2015;4(11):779-94. doi:10.1016/j.molmet.2015.07.010. [PubMed: 26629403]
Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 2006;116(1):115-24. doi:10.1172/JCI24335. [PubMed: 16341265]
Kim J, Chung K, Choi C, Beloor J, Ullah I, Kim N et al. Silencing CCR2 in macrophages alleviates adipose tissue inflammation and the associated metabolic syndrome in dietary obese mice. Mol Ther Nucleic Acids. 2016;5:e280. doi:10.1038/mtna.2015.51. [PubMed: 26812653]
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796-808. doi:10.1172/jci200319246. [PubMed: 14679176]
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821-30. doi:10.1172/jci200319451. [PubMed: 14679177]
Kraakman MJ, Murphy AJ, Jandeleit-Dahm K, Kammoun HL. Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function? Front Immunol. 2014;5:470. doi:10.3389/fimmu.2014.00470. [PubMed: 25309549]
Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E et al. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab. 2014;20(4):614-25. doi:10.1016/j.cmet.2014.08.010. [PubMed: 25242226]
Boutens L, Hooiveld GJ, Dhingra S, Cramer RA, Netea MG, Stienstra R. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses. Diabetologia. 2018;61(4):942-53. doi:10.1007/s00125-017-4526-6. [PubMed: 29333574]
Tiwari P, Blank A, Cui C, Schoenfelt KQ, Zhou G, Xu Y et al. Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer. J Exp Med. 2019;216(6):1345- 58. doi:10.1084/jem.20181616. [PubMed: 31053611]
Henegar C, Tordjman J, Achard V, Lacasa D, Cremer I, Guerre-Millo M et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 2008;9(1):R14. doi:10.1186/gb-2008-9-1-r14. [PubMed: 18208606]
Tanaka M, Ikeda K, Suganami T, Komiya C, Ochi K, Shirakawa I et al. Macrophage-inducible C- type lectin underlies obesity-induced adipose tissue fibrosis. Nature Commun. 2014;5:4982. doi:10.1038/ncomms5982. [PubMed: 25236782]
Chamberlin T, Thompson V, Hillers-Ziemer LE, Walton BN, Arendt LM. Obesity reduces mammary epithelial cell TGFp1 activity through macrophage-mediated extracellular matrix remodeling. FASEB J. 2020. doi:10.1096/fj.202000228RR.
Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K. Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinol. 2007;148(2):868-77. doi:10.1210/en.2006-0687.
Keophiphath M, Achard V, Henegar C, Rouault C, Clement K, Lacasa D. Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol. 2009;23(1):11-24. doi:10.1210/me.2008-0183. [PubMed: 18945811]
Ferrante AW. The immune cells in adipose tissue. Diabetes Obes Metab. 2013;15(0 3):34-8. doi:10.1111/dom.12154. [PubMed: 24003919]
Elgazar-Carmon V, Rudich A, Hadad N, Levy R. Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res. 2008;49(9). doi:10.1194/jlr.M800132- JLR200.
Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nature Med. 2012;18(9). doi:10.1038/nm.2885.
Xia S, Sha H, Yang L, Ji Y, Ostrand-Rosenberg S, Qi L. Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity. J Biol Chem. 2011;286(26):23591-9. doi:10.1074/jbc.M111.237123. [PubMed: 21592961]
Kado T, Nawaz A, Takikawa A, Usui I, Tobe K. Linkage of CD8(+) T cell exhaustion with high- fat diet-induced tumourigenesis. Sci Rep. 2019;9(1):12284. doi:10.1038/s41598-019-48678-0. [PubMed: 31439906]
Reynolds CM, McGillicuddy FC, Harford KA, Finucane OM, Mills KH, Roche HM. Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells-implications for diet-induced insulin resistance. Mol Nutr Food Res. 2012;56(8):1212-22. doi:10.1002/ mnfr.201200058. [PubMed: 22700321]
Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S et al. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes. 2012;61(9):2238-47. doi:10.2337/db11-1274. [PubMed: 22596049]
Stefanovic-Racic M, Yang X, Turner MS, Mantell BS, Stolz DB, Sumpter TL et al. Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes. 2012;61(9):2330-9. doi:10.2337/ db11-1523. [PubMed: 22851575]
Cho KW, Zamarron BF, Muir LA, Singer K, Porsche CE, DelProposto JB et al. Adipose tissue dendritic cells are independent contributors to obesity-induced inflammation and insulin resistance. J Immunol. 2016;197(9):3650-61. doi:10.4049/jimmunol.1600820. [PubMed: 27683748]
Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930-9. doi:10.1038/nm.2002. [PubMed: 19633656]
Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914-20. doi:10.1038/nm.1964. [PubMed: 19633658]
Yang H, Youm YH, Vandanmagsar B, Ravussin A, Gimble JM, Greenway F et al. Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance. J Immunol. 2010;185(3):1836-45. doi:10.4049/jimmunol.1000021. [PubMed: 20581149]
Rausch ME, Weisberg S, Vardhana P, Tortoriello DV. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes. 2008;32(3):451-63. doi:10.1038/sj.ijo.0803744.
Zhang C, Yue C, Herrmann A, Song J, Egelston C, Wang T et al. STAT3 activation-induced fatty acid oxidation in CD8(+) T effector cells is critical for obesity-promoted breast tumor growth. Cell Metab. 2020;31(1):148-61.e5. doi:10.1016/j.cmet.2019.10.013. [PubMed: 31761565]
Zeyda M, Huber J, Prager G, Stulnig TM. Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity. 2011;19(4). doi:10.1038/oby.2010.123.
Travers RL, Motta AC, Betts JA, Bouloumie A, Thompson D. The impact of adiposity on adipose tissue-resident lymphocyte activation in humans. Int J Obesity. 2015;39(5). doi:10.1038/ ijo.2014.195.
Duffaut C, Zakaroff-Girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P et al. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol. 2009;29(10). doi:10.1161/ ATVBAHA.109.192583.
Adhikary S, Hoskin TL, Stallings-Mann ML, Arshad M, Frost MH, Winham SJ et al. Cytotoxic T cell depletion with increasing epithelial abnormality in women with benign breast disease. Breast Cancer Res Treat. 2020;180(1):55-61. doi:10.1007/s10549-019-05493-5. [PubMed: 31933142]