切换至 "中华医学电子期刊资源库"

中华肥胖与代谢病电子杂志 ›› 2023, Vol. 09 ›› Issue (03) : 173 -178. doi: 10.3877/cma.j.issn.2095-9605.2023.03.005

专家论坛

肥胖相关肿瘤研究进展
范晓轩, 王娜, 朱丽花(), 王亮()   
  1. 510630 广州,暨南大学第一附属医院肿瘤科
    510630 广州,暨南大学第一附属医院风湿免疫科
  • 收稿日期:2023-06-08 出版日期:2023-08-30
  • 通信作者: 朱丽花, 王亮
  • 基金资助:
    广州市基础研究计划市校联合资助项目(SL2023A03J01017)

Research progress of obesity-related tumors

Xiaoxuan Fan, Na Wang, Lihua Zhu(), Liang Wang()   

  1. Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
  • Received:2023-06-08 Published:2023-08-30
  • Corresponding author: Lihua Zhu, Liang Wang
引用本文:

范晓轩, 王娜, 朱丽花, 王亮. 肥胖相关肿瘤研究进展[J]. 中华肥胖与代谢病电子杂志, 2023, 09(03): 173-178.

Xiaoxuan Fan, Na Wang, Lihua Zhu, Liang Wang. Research progress of obesity-related tumors[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2023, 09(03): 173-178.

肥胖通过促进慢性系统性炎症、高胰岛素血症、循环类固醇激素升高、血糖和脂质水平升高、促进细胞因子和生长因子的产生等方式促进恶性肿瘤的发生、发展。本文通过对国内外现有文献的回顾,对肥胖相关肿瘤的发生、发展的病理生理机制及减重手术预防肥胖相关肿瘤的现状进行总结。

Obesity can promote the development of tumors through accelerating chronic inflammation, hyperinsulinemia, hypercirculating steroid hormonemia, hypergycemia, hyperlipemia and the production of cytokines and growth factors. Herein, the recent literatures about the development of obesity-related tumors and the phenomenon of obesity paradox are reviewed briefly. And we summarize the current status of bariatric surgery to prevent obesity-related tumors.

图1 肥胖相关肿瘤的发生机制
[1]
Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013 [J]. The Lancet, 2014, 384(9945): 766-781.
[2]
Bhaskaran K, Douglas I, Forbes H, et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults [J]. The Lancet, 2014, 384(9945): 755-765.
[3]
Arnold M, Pandeya N, Byrnes G, et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study [J]. The Lancet Oncology, 2015, 16(1): 36-46.
[4]
Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer — Viewpoint of the IARC Working Group [J]. New England Journal of Medicine, 2016, 375(8): 794-798.
[5]
Hotamisligil GS. Inflammation and metabolic disorders [J]. Nature, 2006, 444(7121): 860-867.
[6]
Kryston TB, Georgiev AB, Pissis P, et al. Role of oxidative stress and DNA damage in human carcinogenesis [J]. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2011, 711(1-2): 193-201.
[7]
Savini I, Catani M, Evangelista D, et al. Obesity-Associated Oxidative Stress: Strategies Finalized to Improve Redox State [J]. International Journal of Molecular Sciences, 2013, 14(5): 10497-10538.
[8]
Luperini BCO, Almeida DC, Porto MP, et al. Gene polymorphisms and increased DNA damage in morbidly obese women [J]. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2015, 776(1-2): 111-117.
[9]
Pelucchi C, Serraino D, Negri E, et al. The Metabolic Syndrome and Risk of Prostate Cancer in Italy [J]. Annals of Epidemiology, 2011, 21(11): 835-841.
[10]
Tian Y, Wang K, Li J, et al. The association between serum lipids and colorectal neoplasm: a systemic review and meta-analysis [J]. Public Health Nutrition, 2015, 18(18): 3355-3370.
[11]
Gallagher EJ, Zelenko Z, Neel BA, et al. Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia [J]. Oncogene, 2017, 36(46): 6462-6471.
[12]
Jin Y, Yang T, Li D, et al. Effect of dietary cholesterol intake on the risk of esophageal cancer: a meta-analysis [J]. Journal of International Medical Research, 2019, 47(9): 4059-4068.
[13]
Ringel AE, Drijvers JM, Baker GJ, et al. Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity [J]. Cell, 2020, 183(7): 1848-1866. e26.
[14]
Danilo C, Gutierrez-Pajares JL, Mainieri MA, et al. Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development [J]. Breast Cancer Research, 2013, 15(5): R87.
[15]
Gordon JA, Noble JW, Midha A, et al. Upregulation of Scavenger Receptor B1 Is Required for Steroidogenic and Nonsteroidogenic Cholesterol Metabolism in Prostate Cancer [J]. Cancer Research, 2019, 79(13): 3320-3331.
[16]
Guillaumond F, Bidaut G, Ouaissi M, et al. Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma [J]. Proceedings of the National Academy of Sciences, 2015, 112(8): 2473-2478.
[17]
Graziani SR, Igreja FAF, Hegg R, et al. Uptake of a Cholesterol-Rich Emulsion by Breast Cancer [J]. Gynecologic Oncology, 2002, 85(3): 493-497.
[18]
Pascual G, Avgustinova A, Mejetta S, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36 [J]. Nature, 2017, 541(7635): 41-45.
[19]
Ladanyi A, Mukherjee A, Kenny HA, et al. Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis [J]. Oncogene, 2018, 37(17): 2285-2301.
[20]
Michelet X, Dyck L, Hogan A, et al. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses [J]. Nature Immunology, 2018, 19(12): 1330-1340.
[21]
Wang H, Franco F, Tsui Y-C, et al. CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors [J]. Nature Immunology, 2020, 21(3): 298-308.
[22]
Iyengar P, Espina V, Williams TW, et al. Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment [J]. Journal of Clinical Investigation, 2005, 115(5): 1163-1176.
[23]
Sheng X, Parmentier J-H, Tucci J, et al. Adipocytes Sequester and Metabolize the Chemotherapeutic Daunorubicin [J]. Molecular Cancer Research, 2017, 15(12): 1704-1713.
[24]
Su F, Ahn S, Saha A, et al. Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance [J]. Oncogene, 2019, 38(11): 1979-1988.
[25]
Reggiani F, Labanca V, Mancuso P, et al. Adipose Progenitor Cell Secretion of GM-CSF and MMP9 Promotes a Stromal and Immunological Microenvironment That Supports Breast Cancer Progression [J]. Cancer Research, 2017, 77(18): 5169-5182.
[26]
Saha A, Ahn S, Blando J, et al. Proinflammatory CXCL12-CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice [J]. Cancer Research, 2017, 77(18): 5158-5168.
[27]
Qian B-Z, Pollard JW. Macrophage Diversity Enhances Tumor Progression and Metastasis [J]. Cell, 2010, 141(1): 39-51.
[28]
Arendt LM, McCready J, Keller PJ, et al. Obesity Promotes Breast Cancer by CCL2-Mediated Macrophage Recruitment and Angiogenesis [J]. Cancer Research, 2013, 73(19): 6080-6093.
[29]
Kuang D-M, Zhao Q, Peng C, et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1 [J]. Journal of Experimental Medicine, 2009, 206(6): 1327-1337.
[30]
Springer NL, Iyengar NM, Bareja R, et al. Obesity-Associated Extracellular Matrix Remodeling Promotes a Macrophage Phenotype Similar to Tumor-Associated Macrophages [J]. The American Journal of Pathology, 2019, 189(10): 2019-2035.
[31]
Iyengar NM, Zhou XK, Gucalp A, et al. Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer [J]. Clinical Cancer Research, 2016, 22(9): 2283-2289.
[32]
Morris PG, Hudis CA, Giri D, et al. Inflammation and Increased Aromatase Expression Occur in the Breast Tissue of Obese Women with Breast Cancer [J]. Cancer Prevention Research, 2011, 4(7): 1021-1029.
[33]
Bowers LW, Brenner AJ, Hursting SD, et al. Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production [J]. Breast Cancer Research and Treatment, 2015, 149(1): 49-57.
[34]
Maffei M, Halaas J, Ravussin E, et al. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects [J]. Nature Medicine, 1995, 1(11): 1155-1161.
[35]
Andò S, Gelsomino L, Panza S, et al. Obesity, Leptin and Breast Cancer: Epidemiological Evidence and Proposed Mechanisms [J]. Cancers, 2019, 11(1): 62.
[36]
Zheng Q, Dunlap SM, Zhu J, et al. Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor growth in obese mice and abrogates tumor initiating cell survival [J]. Endocrine-Related Cancer, 2011, 18(4): 491-503.
[37]
Wang Z, Aguilar EG, Luna JI, et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade [J]. Nature Medicine, 2019, 25(1): 141-151.
[38]
Murphy KA, James BR, Sjaastad FV, et al. Cutting Edge: Elevated Leptin during Diet-Induced Obesity Reduces the Efficacy of Tumor Immunotherapy [J]. The Journal of Immunology, 2018, 201(7): 1837-1841.
[39]
Wrann CD, Laue T, Hübner L, et al. Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions [J]. American Journal of Physiology-Endocrinology and Metabolism, 2012, 302(1): E108-E116.
[40]
Sepesi B, Gold K A, Correa A M, et al. The Influence of Body Mass Index on Overall Survival Following Surgical Resection of Non–Small Cell Lung Cancer [J]. Journal of Thoracic Oncology, 2017, 12(8): 1280-1287.
[41]
McQuade JL, Daniel CR, Hess KR, et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis [J]. The Lancet Oncology, 2018, 19(3): 310-322.
[42]
Kichenadasse G, Miners JO, Mangoni AA, et al. Association Between Body Mass Index and Overall Survival With Immune Checkpoint Inhibitor Therapy for Advanced Non–Small Cell Lung Cancer [J]. JAMA Oncology, 2020, 6(4): 512.
[43]
Webb PM. Commentary: Weight gain, weight loss, and endometrial cancer[J]. International Journal of Epidemiology, 2006, 35(1): 166-168.
[44]
Sjöström L, Larsson B, Carlsson B, et al. Effects of Bariatric Surgery on Mortality in Swedish Obese Subjects [J]. New England Journal of Medicine, 2007, 357(8): 741-752.
[45]
Adams TD, Stroup AM, Gress RE, et al. Cancer Incidence and Mortality After Gastric Bypass Surgery [J]. Obesity, 2009, 17(4): 796-802.
[46]
Aminian A, Wilson R, Al-Kurd A, et al. Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity [J]. JAMA, 2022, 327(24): 2423.
[47]
Bonovas S, Filioussi K, Sitaras NM. Statin use and the risk of prostate cancer: A metaanalysis of 6 randomized clinical trials and 13 observational studies: Statin Use and Prostate Cancer Risk [J]. International Journal of Cancer, 2008, 123(4): 899-904.
[48]
Manthravadi S, Shrestha A, Madhusudhana S. Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta-analysis: Breast cancer: A systematic review and meta-analysis [J]. International Journal of Cancer, 2016, 139(6): 1281-1288.
[49]
Scully T, Ettela A, LeRoith D, et al. Obesity, Type 2 Diabetes, and Cancer Risk [J]. Frontiers in Oncology, 2021, 10: 615375.
[50]
Lengyel E, Makowski L, DiGiovanni J, et al. Cancer as a Matter of Fat: The Crosstalk between Adipose Tissue and Tumors [J]. Trends in Cancer, 2018, 4(5): 374-384.
[51]
Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression [J]. Nature Reviews Endocrinology, 2019, 15(3): 139-154.
[52]
Stancu C, Sima A. Statins: mechanism of action and effects [J]. Journal of Cellular and Molecular Medicine, 2001, 5(4): 378-387.
[53]
Murtola TJ, Syvälä H, Pennanen P, et al. The Importance of LDL and Cholesterol Metabolism for Prostate Epithelial Cell Growth [J]. I. Agoulnik. PLoS ONE, 2012, 7(6): e39445.
[1] 何金梅, 尹立雪, 谭静, 张文军, 王锐, 任梅, 廖明娇. 超声心肌做功技术对2型糖尿病患者潜在左心室心肌收缩功能损伤的评价[J]. 中华医学超声杂志(电子版), 2023, 20(10): 1029-1035.
[2] 韩丹, 王婷, 肖欢, 朱丽容, 陈镜宇, 唐毅. 超声造影与增强CT对儿童肝脏良恶性病变诊断价值的对比分析[J]. 中华医学超声杂志(电子版), 2023, 20(09): 939-944.
[3] 姚宏伟, 魏鹏宇, 高加勒, 张忠涛. 不断提高腹腔镜右半结肠癌D3根治术的规范化[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 1-4.
[4] 杜晓辉, 崔建新. 腹腔镜右半结肠癌D3根治术淋巴结清扫范围与策略[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 5-8.
[5] 周岩冰, 刘晓东. 腹腔镜右半结肠癌D3根治术消化道吻合重建方式的选择[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 9-13.
[6] 唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[7] 张生军, 赵阿静, 李守博, 郝祥宏, 刘敏丽. 高糖通过HGF/c-met通路促进结直肠癌侵袭和迁移的实验研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 21-24.
[8] 张焱辉, 张蛟, 朱志贤. 留置肛管在中低位直肠癌新辅助放化疗后腹腔镜TME术中的临床研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 25-28.
[9] 李凤仪, 李若凡, 高旭, 张超凡. 目标导向液体干预对老年胃肠道肿瘤患者术后血流动力学、胃肠功能恢复的影响[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 29-32.
[10] 李建美, 邓静娟, 杨倩. 两种术式联合治疗肝癌合并肝硬化门静脉高压的安全性及随访评价[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 41-44.
[11] 燕速, 霍博文, 徐惠宁. 4K荧光腹腔镜扩大右半结肠CME+D3根治术及No.206、No.204组淋巴结清扫术[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 14-14.
[12] 钱龙, 陆晓峰, 王行舟, 杜峻峰, 沈晓菲, 管文贤. 神经系统调控胃肠道肿瘤免疫应答研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 86-89.
[13] 曹长青, 郭新艳, 高源, 张存, 唐海利, 樊东, 杨小军, 张松, 赵华栋. 肿瘤微环境参与介导HER2阳性乳腺癌曲妥珠单抗耐药的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 90-95.
[14] 纪凯伦, 郝少龙, 孙海涛, 韩威. 减重术后胆囊结石形成机制的新进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 100-103.
[15] 徐军, 姬园园, 陈君平, 王健. 伴菊形团结构的脑膜瘤合并颅骨侵犯一例并文献复习[J]. 中华临床医师杂志(电子版), 2023, 17(08): 916-919.
阅读次数
全文


摘要