Tumor-stroma crosstalk对肝细胞癌中肝星状细胞氨基酸代谢水平的影响

吴静; 孟庆华; 薛冉

doi:10.3969/j.issn.1001-5256.2018.12.020

Tumor-stroma crosstalk对肝细胞癌中肝星状细胞氨基酸代谢水平的影响

DOI: 10.3969/j.issn.1001-5256.2018.12.020

1. 首都医科大学附属北京佑安医院肝病重症医学科
2. 首都医科大学附属北京朝阳医院消化内科

基金项目:

首都卫生发展科研专项(2016-1-2181)；

详细信息

中图分类号: R735.7
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出版历程
- 出版日期: 2018-12-20

Effect of tumor-stroma crosstalk on amino acid metabolism in hepatic stellate cells

Research funding:

摘要

摘要: 目的探讨tumor-stroma crosstalk对肝星状细胞（HSC）氨基酸代谢的影响。方法分别培养人肝癌细胞系HepG2、Hep3B、Huh7,以及LX-2 HSC。分别使用LX-2 HSC条件培养基（LX2-CM）和HepG2、Hep3B、Huh7肝癌细胞混合条件培养基（Hep-CM）培养HSC,并收集细胞上清,应用氨基酸分析仪检测细胞上清氨基酸谱变化。计量资料组间比较采用t检验。结果HSC氨基酸代谢水平改变情况,与对照组（LX2-CM）相比,实验组（Hep-CM）上清中瓜氨酸（t=3. 426,P=0. 027）、缬氨酸（t=2. 892,P=0. 045）、异亮氨酸（t=4. 224,P=0. 013）、亮氨酸（t=4. 150,P=0. 014）、酪氨酸（t=3. 556,P=0. 024）、苯丙氨酸（t=4. 023,P=0. 016）、赖氨酸（t=3. 369,P=0. 028）水平降低,差异均有统计学意义。结论肿瘤微环境中,tumor-stroma crosstalk可以影响HSC的氨基酸代谢水平,这种改变可能反过来促使肝癌细胞更加适应低氧微环境。
- 肝肿瘤 /
- 氨基酸类 /
- 代谢 /
- tumor-stroma crosstalk
Abstract: Objective To investigate the effect of tumor-stroma crosstalk on amino acid metabolism in hepatic stellate cells (HSCs) .Methods Human hepatoma cell lines HepG2, Hep3 B, and Huh7 and the HSC LX-2 were cultured separately. HSCs were cultured in HSC LX-2 conditioned medium (LX2-CM) and HepG2/Hep3 B/Huh7 mixed conditioned medium (Hep-CM) , respectively. The supernatants were collected and an amino acid analyzer was used to measure the change in aminogram. The t-test was used for comparison of continuous data between groups. Results There was a significant change in amino acid metabolism in HSCs. Compared with the LX2-CM control group, the Hep-CM experimental group had significant reductions in the levels of citrulline (t = 3. 426, P = 0. 027) , valine (t = 2.892, P = 0. 045) , isoleucine (t = 4. 224, P = 0. 013) , leucine (t = 4. 150, P = 0. 014) , tyrosine (t = 3. 556, P = 0. 024) , phenylalanine (t = 4. 023, P = 0. 016) , and lysine (t = 3. 369, P = 0. 028) in cell supernatant. Conclusion Tumor-stroma crosstalk can influence amino acid metabolism in HSCs in tumor microenvironment, and such change in turn makes hepatoma cells better adapted to hypoxic microenvironment.
- liver neoplasms /
- amino acids /
- metabolism /
- tumor-stroma crosstalk

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参考文献(17)

[1] HAN MS, M00N KS, LEE KH, et al. Brain metastasis from hepatocellular carcinoma:The role of surgery as a prognostic factor[J].BMC Cancer, 2013, 13:567.

[2] National Health and Family Planning Commission of the People's Republic of China. Diagnosis, management, and treatment of hepatocellular carcinoma (V2017) [J]. J Clin Hepatol, 2017, 33 (8) :1419-1431. (in Chinese) 中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范 (2017年版) [J].临床肝胆病杂志, 2017, 33 (8) :1419-1431.

[3] HARRIS AL. Hypoxia——a key regulatory factor in tumour growth[J].Nat Rev Cancer, 2002, 2 (1) :38-47.

[4] LU W, QIAN SC, WANG FM, et al. Metabolism of animo acid in human liver cancer cell line in vitro[J]. Tianjin Med J, 2002, 30 (11) :643-645. (in Chinese) 陆伟, 钱绍诚, 王凤梅, 等.人肝癌细胞体外氨基酸代谢[J].天津医药, 2002, 30 (11) :643-645.

[5] ISHIKAWA T. Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma[J]. World J Gastroenterol, 2012, 18 (17) :2005-2008.

[6] MARTINEZ-OUTSCHOORN UE, PESTELL RG, HOWELL A, et al.Energy transfer in"parasitic"cancer metabolism:Mitochondria are the powerhouse and Achilles'heel of tumor cells[J]. Cell Cycle, 2011, 10 (24) :4208-4016.

[7] HOY AJ, BALABAN S, SAUNDERS DN. Adipocyte-tumor cell metabolic crosstalk in breast cancer[J]. Trends Mol Med, 2017, 23 (5) :381-392.

[8] FUNG C, LOCK R, GAO S, et al. Induction of autophagy during extracellular matrix detachment promotes cell survival[J]. Mol Biol Cell, 2008, 19 (3) :797-806.

[9] VAUPEL P, MAYER A. Hypoxia and anemia:Effects on tumor biology and treatment resistance[J]. Transfus Clin Biol, 2005, 12 (1) :5-10.

[10] ZHAO YP, HAN XQ, XUE SB, et al. Clinical analysis of blood amino acids and trace elements in patients with hepatocellular carcinoma[J]. J Clin Hepatol, 2015, 31 (6) :915-917. (in Chinese) 赵玉萍, 韩秀青, 薛书保, 等.原发性肝癌患者血中微量元素与氨基酸浓度的变化分析[J].临床肝胆病杂志, 2015, 31 (6) :915-917.

[11] MIZUNO Y, SHU S, AKIYAMA Y, et al. DEPDC5 deficiency contributes to resistance to leucine starvation via p62 accumulation in hepatocellular carcinoma[J]. Sci Rep, 2018, 8:106.

[12] YANG J, LU W, ZOU MY, et al. Plasma and tamor tissue amino acid changes in hepatoma-bearing mice[J]. J Clin Hepatol, 2006, 9 (1) :22-24. (in Chinese) 杨晶, 陆伟, 邹满意, 等.荷肝癌小鼠血浆和肿瘤组织游离氨基酸代谢变化及其与肿瘤体积相关性研究[J].实用肝脏病杂志, 2006, 9 (1) :22-24.

[13] NISHIHIRA T, TAKAGI T, KAWARABAYASHI Y, et al. Anticancer therapy with valine-depleted amino acid imbalance solution[J]. Tohoku J Exp Med, 1988, 156 (3) :259-270.

[14] SHARMA B, SINGH S, KANWAR SS. L-Methionase:A therapeutic enzyme to treat malignancies[J]. Biomed Res Int, 2014, 2014 (3) :506287.

[15] ZHU HK. Clinical value of citrulline in evaluating intestinal impairment in patients with sepsis[C]. Collected papers from The 2014Tenth National Academic Conference on Integrated Traditional Chinese and Western Medicine and Disaster Medicine, Founding Conference of Professional Committee on Disaster Medicine and Critical Care Medicine of Jiangsu Provincial Society of Integrated Traditional Chinese and Western Medicine&Health Industry Achievement Exhibition and Negotiation Meeting, 2014:3. (in Chinese) 朱宏坤.瓜氨酸在脓毒症患者肠功能损伤评估中的临床价值[C]. 2014第十届全国中西医结合灾害医学学术大会江苏省中西医结合学会灾害医学、重症医学专业委员会成立大会暨健康产业成果展示洽谈会学术论文集, 2014:3.

[16] DIETRICH CG, GOTZE O, GEIER A. Molecular changes in hepatic metabolism and transportin cirrhosis and their functional importance[J]. World J Gastroenterol, 2016, 22 (1) :72-88.

[17] YI M, XIANG B, LI XL, et al. Metabolic reprogramming in cancer:The art of balance[J]. J Cent South Univ:Med Sci, 2013, 38 (11) :1177-1187. (in Chinese) 易梅, 向波, 李小玲, 等.代谢重编程:肿瘤的平衡之舞[J].中南大学学报:医学版, 2013, 38 (11) :1177-1187.

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