肿瘤相关成纤维细胞与肝癌的关系

胡晓; 毛德文; 牙程玉

doi:10.3969/j.issn.1001-5256.2021.02.041

肿瘤相关成纤维细胞与肝癌的关系

DOI: 10.3969/j.issn.1001-5256.2021.02.041

1.
广西中医药大学研究生学院，南宁 530001
2.
广西中医药大学第一附属医院肝病一区，南宁 530023

基金项目:

国家自然科学基金面上项目 (81774236);

国家自然科学基金 (81460718);

国家“十三五”艾滋病和病毒性肝炎等重大传染病防治科技重大专项 (2018ZX10725504-001-008);

广西研究生教育创新计划资助项目 (YCSY2020090)

作者贡献声明：胡晓负责拟定写作思路，撰写文章并最后定稿；毛德文教授负责对文章的知识性内容做批判性审阅；牙程玉参与文章修订。

详细信息

作者简介:
胡晓(1994—)，女，主要从事中医药防治肝病的研究

通信作者:
毛德文，mdwboshi2005@163.com

中图分类号: R735.7
计量
- 文章访问数: 438
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- PDF下载量: 49
- 被引次数: 0
出版历程
- 收稿日期: 2020-08-07
- 录用日期: 2020-09-11
- 出版日期: 2021-02-20

Association between cancer-associated fibroblasts and liver cancer

Xiao HU¹,
Dewen MAO^{2
, ,},
Chengyu YA¹

1.
Graduate School, Guangxi University of Chinese Medicine, Nanning 530001, China
2.
First Ward of Liver Diseases, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China

摘要

摘要: 我国肝病多发，肝癌一直是国民健康的一大威胁，目前临床针对肝癌的防治手段效果欠佳，随着研究的不断深入，学者们将焦点转向了肿瘤微环境中的肿瘤相关成纤维细胞，越来越多的证据表明肿瘤相关成纤维细胞或可为肝癌防治提供全新靶位。现就肿瘤相关成纤维细胞在肝癌发生发展中的作用及在肝癌治疗中的潜力作一综述。
- 肝肿瘤 /
- 癌相关成纤维细胞 /
- 肿瘤微环境
Abstract: Liver cancer has always been a threat to national health since liver disease has a high incidence rate in China. At present, methods for the prevention and treatment of liver cancer have unsatisfactory effects in clinical practice, and with in-depth studies, scholars have changed their focus to cancer-associated fibroblasts (CAFs) in tumor microenvironment. More and more evidence has shown that CAFs may provide a new target for the prevention and treatment of liver cancer. This article summarizes the role of CAFs in the development and progression of liver cancer and the potential of CAFs in the treatment of liver cancer.
- Liver Neoplasms /
- Cancer-Associated Fibroblasts /
- Tumor Microenvironment

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参考文献(35)

[1]	Department of Medical Administration, National Health and Health Commission of the People's Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)[J]. J Clin Hepatol, 2020, 36(2): 277-292. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.02.007 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2020, 36(2): 277-292. DOI: 10.3969/j.issn.1001-5256.2020.02.007
[2]	LIU LY, LIU KK, ZHANG WW, et al. Advances in the role of cytokines secreted by tumor-associated macrophages in tumor microenvironment[J]. China Med Herald, 2019, 16(11): 30-33. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201911008.htm 刘璐瑶, 刘可可, 张雯雯, 等. 肿瘤相关巨噬细胞分泌的细胞因子在肿瘤微环境中作用的研究进展[J]. 中国医药导报, 2019, 16(11): 30-33. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201911008.htm
[3]	ARNETH B. Tumor microenvironment[J]. Medicina (Kaunas), 2019, 56(1): 15. DOI: 10.3390/medicina56010015
[4]	HUANG SJ, QIU XD, LI WY, et al. Cellular crosstalk and tumorigenic mechanisms in tumor microenvironment[J]. Chin Bull Life Sci, 2020, 32(4): 315-324. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-SMKX202004003.htm 黄思佳, 邱旭东, 李文彦, 等. 肿瘤微环境中的细胞调控网络及促瘤机制[J]. 生命科学, 2020, 32(4): 315-324. https://www.cnki.com.cn/Article/CJFDTOTAL-SMKX202004003.htm
[5]	ZHANG WW, LIU KK, LIU LY, et al. Advance research on the role of cancer -associated fibroblasts in oral squamous cell carcinoma and its targeted therapy[J]. China Med Herald, 2019, 16(14): 29-32. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201914009.htm 张雯雯, 刘可可, 刘璐瑶, 等. 肿瘤相关成纤维细胞在口腔鳞状细胞癌中的作用及其靶向治疗的研究进展[J]. 中国医药导报, 2019, 16(14): 29-32. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201914009.htm
[6]	AFFO S, YU LX, SCHWABE RF. The role of cancer-associated fibroblasts and fibrosis in liver cancer[J]. Annu Rev Pathol, 2017, 12: 153-186. DOI: 10.1146/annurev-pathol-052016-100322
[7]	FENG RX, CHEN S, LIU J, et al. Effect of cancer-associated fibroblasts on cancer stem cells in hepatocellular carcinoma[J]. Chin J Gastroenter, 2016, 21(9): 517-522. (in Chinese) DOI: 10.3969/j.issn.1008-7125.2016.09.002 冯仁鑫, 陈升, 刘娇, 等. 肿瘤相关成纤维细胞对肝癌干细胞的影响[J]. 胃肠病学, 2016, 21(9): 517-522. DOI: 10.3969/j.issn.1008-7125.2016.09.002
[8]	LI Y, WANG R, XIONG S, et al. Cancer-associated fibroblasts promote the stemness of CD24⁺ liver cells via paracrine signaling[J]. J Mol Med (Berl), 2019, 97(2): 243-255. DOI: 10.1007/s00109-018-1731-9
[9]	SHA M, JEONG S, GU JY, et al. Isolation, purification and identification of human intrahepatic cholangiocarcinoma-associated fibroblasts and its effect on proliferation and migration of cholangiocarcinoma cells[J]. Chin Hepatol, 2017, 22(6): 517-522. (in Chinese) DOI: 10.3969/j.issn.1008-1704.2017.06.013 沙朦, Jeong Seogsong, 顾劲扬, 等. 人肝内胆管癌相关成纤维细胞的分离、纯化和鉴定及对胆管癌细胞生长和迁移的影响[J]. 肝脏, 2017, 22(6): 517-522. DOI: 10.3969/j.issn.1008-1704.2017.06.013
[10]	SUN HR, ZHANG Y, DU LB, et al. Isolation, culture and identification of hepatocellular carcinoma-associated fibroblast and its effect on the biological function of hepatocellular carcinoma cells[J]. Cancer Res Clinic, 2017, 29(8): 505-509. (in Chinese) DOI: 10.3760/cma.j.issn.1006-9801.2017.08.001 孙浩然, 张钰, 杜鲁巴, 等. 肝癌中肿瘤相关成纤维细胞的分离、培养、鉴定及其对肝癌细胞生物学功能的影响[J]. 肿瘤研究与临床, 2017, 29(8): 505-509. DOI: 10.3760/cma.j.issn.1006-9801.2017.08.001
[11]	LAU EY, LO J, CHENG BY, et al. Cancer-associated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular carcinoma through c-Met/FRA1/HEY1 signaling[J]. Cell Rep, 2016, 15(6): 1175-1189. DOI: 10.1016/j.celrep.2016.04.019
[12]	DENG Y, CHENG J, FU B, et al. Hepatic carcinoma-associated fibroblasts enhance immune suppression by facilitating the generation of myeloid-derived suppressor cells[J]. Oncogene, 2017, 36(8): 1090-1101. DOI: 10.1038/onc.2016.273
[13]	LIU Z, CHEN M, ZHAO R, et al. CAF-induced placental growth factor facilitates neoangiogenesis in hepatocellular carcinoma[J]. Acta Biochim Biophys Sin (Shanghai), 2020, 52(1): 18-25. DOI: 10.1093/abbs/gmz134
[14]	HUANG B, HUANG M, LI Q. Cancer-associated fibroblasts promote angiogenesis of hepatocellular carcinoma by VEGF-mediated EZH2/VASH1 pathway[J]. Technol Cancer Res Treat, 2019, 18: 1533033819879905.
[15]	LU Y, LIN N, CHEN ZJ, et al. Correlation between human hepatocellular carcinoma associated fibroblast and angiogenesis in hepatocellular carcinoma[J/CD]. Chin J Hepat Surg (Electronic Edition), 2017, 6(3): 228-232. (in Chinese) 卢逸, 林楠, 陈之巨, 等. 人肝癌相关成纤维细胞与肝癌血管生成的相关性研究[J/CD]. 中华肝脏外科手术学电子杂志, 2017, 6(3): 228-232.
[16]	LI Y, XU YJ, BAO ML. Expression of hepatoma-associated fibroblasts in human hepatocellular carcinoma tissues and its relationship with microvessel density[J]. Shanghai Med J, 2018, 41(6): 344-348. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-SHYX201806010.htm 李艳, 徐永建, 鲍明亮. 肝癌相关成纤维细胞在人肝细胞癌组织中的表达情况及其与微血管密度的关系[J]. 上海医学, 2018, 41(6): 344-348. https://www.cnki.com.cn/Article/CJFDTOTAL-SHYX201806010.htm
[17]	ZHANG X, ZHANG J, ZHOU H, et al. Molecular mechanisms and anticancer therapeutic strategies in vasculogenic mimicry[J]. J Cancer, 2019, 10(25): 6327-6340. DOI: 10.7150/jca.34171
[18]	HE XJ, ZHANG ZS, CHEN GY, et al. Predictive value of vasculogenic mimicry in transcatheter arterial chemoembolization on primary hepatocellularcarcinoma[J]. J Lanzhou Univ (Medical Sciences), 2020, 46(1): 30-35, 41. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-LZYX202001007.htm 何学军, 张志胜, 陈高阳, 等. 血管拟态在原发性肝癌经动脉栓塞化疗疗效及预后中的评估价值[J]. 兰州大学学报(医学版), 2020, 46(1): 30-35, 41. https://www.cnki.com.cn/Article/CJFDTOTAL-LZYX202001007.htm
[19]	TAO MZ, HU SY, GUO QX, et al. Relationship and clinical significance between α-SMA+ CAFs in hepatocellular carcinoma tissues and vasculogenic mimicry[J]. J Mod Oncol, 2019, 27(23): 4234-4237. (in Chinese) DOI: 10.3969/j.issn.1672-4992.2019.23.025 陶明珠, 胡书娅, 郭庆喜, 等. 肝细胞癌组织中肿瘤相关成纤维细胞与血管生成拟态的相关性及临床意义[J]. 现代肿瘤医学, 2019, 27(23): 4234-4237. DOI: 10.3969/j.issn.1672-4992.2019.23.025
[20]	YANG J, LU Y, LIN YY, et al. Vascular mimicry formation is promoted by paracrine TGF-β and SDF1 of cancer-associated fibroblasts and inhibited by miR-101 in hepatocellular carcinoma[J]. Cancer Lett, 2016, 383(1): 18-27. DOI: 10.1016/j.canlet.2016.09.012
[21]	HUA XF, LI TJ, JIA CC, et al. Effect of hepatocellular carcinoma associated fibroblasts to hepatocellular carcinoma[J/CD]. Chin J Hepat Surg (Electronic Edition), 2013, 2(3): 194-199. (in Chinese) 华学锋, 李团结, 贾昌昌, 等. 肝癌相关成纤维细胞对肝细胞肝癌影响的实验研究[J/CD]. 中华肝脏外科手术学电子杂志, 2013, 2(3): 194-199.
[22]	FANG T, LV H, LV G, et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer[J]. Nat Commun, 2018, 9(1): 191. DOI: 10.1038/s41467-017-02583-0
[23]	ZHANG Z, LI X, SUN W, et al. Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis[J]. Cancer Lett, 2017, 397: 33-42. DOI: 10.1016/j.canlet.2017.03.004
[24]	SHA M, JEONG S, QIU BJ, et al. Isolation of cancer-associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma[J]. Cancer Med, 2018, 7(9): 4665-4677. DOI: 10.1002/cam4.1704
[25]	ZHANG XF, DONG M, PAN YH, et al. Expression pattern of cancer-associated fibroblast and its clinical relevance in intrahepatic cholangiocarcinoma[J]. Hum Pathol, 2017, 65: 92-100. DOI: 10.1016/j.humpath.2017.04.014
[26]	WU W, MENG N, PAN ZJ, et al. Cancer associated fibroblasts promotes cancer metastasis in cholangiocarcinoma RBE cells[J]. Chin J Exp Surg, 2019, 36(7): 1211-1214. (in Chinese) 武伟, 孟柠, 潘志坚, 等. 胆管癌相关成纤维细胞对人胆管癌细胞转移的影响[J]. 中华实验外科杂志, 2019, 36(7): 1211-1214.
[27]	LIU J, CHEN S, WANG W, et al. Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways[J]. Cancer Lett, 2016, 379(1): 49-59.
[28]	SUN L, WANG Y, WANG L, et al. Resolvin D1 prevents epithelial-mesenchymal transition and reduces the stemness features of hepatocellular carcinoma by inhibiting paracrine of cancer-associated fibroblast-derived COMP[J]. J Exp Clin Cancer Res, 2019, 38(1): 170.
[29]	WANG Y, GAN G, WANG B, et al. Cancer-associated fibroblasts promote irradiated cancer cell recovery through autophagy[J]. EBioMedicine, 2017, 17: 45-56.
[30]	ZHAO Z, BAI S, WANG R, et al. Cancer-associated fibroblasts endow stem-like qualities to liver cancer cells by modulating autophagy[J]. Cancer Manag Res, 2019, 11: 5737-5744.
[31]	MADSEN CD, PEDERSEN JT, VENNING FA, et al. Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis[J]. EMBO Rep, 2015, 16(10): 1394-1408.
[32]	MERTENS JC, FINGAS CD, CHRISTENSEN JD, et al. Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma[J]. Cancer Res, 2013, 73(2): 897-907.
[33]	YU L, LIU Q, HUO J, et al. Cancer-associated fibroblasts induce immunotherapy resistance in hepatocellular carcinoma animal model[J]. Cell Mol Biol (Noisy-le-grand), 2020, 66(2): 36-40.
[34]	TAN J, YANG YT, SUN WJ, et al. The functional heterogeneity and source diversity of cancer associated fibroblasts[J]. Chin J Pathol, 2020, 49(7): 764-767. (in Chinese) 谈静, 杨玉婷, 孙文杰, 等. 癌相关成纤维细胞的功能异质性与来源多样性[J]. 中华病理学杂志, 2020, 49(7): 764-767.
[35]	GAO YJ, YAO Y, SONG QB, et al. Research progress in activation mechanism of cancer-associated fibroblasts[J]. J Chin Oncol, 2019, 25(5): 453-457. (in Chinese)