肝星状细胞在肝细胞癌形成和发展中的作用

陈启明; 陈青锋

doi:10.3969/j.issn.1001-5256.2014.03.023

肝星状细胞在肝细胞癌形成和发展中的作用

DOI: 10.3969/j.issn.1001-5256.2014.03.023

兰州大学第一医院

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中图分类号: R575.2
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出版历程
- 出版日期: 2014-03-20

The role of hepatic stellate cells in development and progression of hepatocellular carcinoma

摘要

摘要:
肿瘤的发生、侵袭及转移是长久以来备受关注的问题,肿瘤细胞与其周围基质物质的关系作为其中的关键因素愈加收到重视,肝星状细胞（HSC）作为肝癌微环境中的重要组成部分,在"炎症-肝纤维化/肝硬化-肿瘤"这一发生发展过程中充当了重要的介质。介绍了HSC的来源及其活化过程,并进一步阐述HSC自身与其分泌的多种细胞因子在肝细胞癌增殖、迁移、侵袭过程中对机体免疫反应发挥的作用。认为HSC不仅是肿瘤生长的"温床",也为肿瘤抵御了免疫系统的追踪和清除。因此在单一抗肿瘤治疗无法取得明显效果时,对于肝癌微环境的多方位治疗成为值得探讨的方案。
- 癌,肝细胞 /
- 脂细胞 /
- 细胞因子类 /
- 综述
Abstract:
A growing body of literature highlights the cross- talk between tumor cells and the surrounding peritumoral stroma as a key modulator in the development, invasion, and metastasis of hepatocellular carcinoma ( HCC) . Hepatic stellate cells ( HSC) , an important component in the microenvironment of HCC, play an important role in the development and progression of “inflammation- fibrosis / cirrhosis-tumor”. The origin and activation of HSC, as well as the effects of HSC and their cytokines on the immune response in the proliferation, metastasis, and invasion of HCC, are reviewed. It is thought that HSC are not only a“hotbed”for tumor growth, but also help resist the tumor tracing and elimination mechanism of the immune system. Therefore, it is worth developing treatments targeting the tumor microenvironment when the single anti- cancer therapy is ineffective.
- carcinoma, hepatocellular /
- adipocytes /
- cytokines /
- review

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参考文献(36)

[1]YANG X, LI YJ.Effect of spleen-strengthening and qi-benefiting therapy on immune microenvironment of primary liver cancer[J].Jilin J Tradit Chin Med, 2013, 33 (1) :9-11. (in Chinese) 杨欣, 李涌健.健脾益气法对原发性肝癌免疫微环境影响的研究[J].吉林中医药, 2013, 33 (1) :9-11.

[2]FAOUZI S, LE BAIL B, NEAUD V, et al.Myofibroblasts are responsible for collagen synthesis in the stroma of human hepatocellular carcinoma:an in vivo and in vitro study[J].J Hepatol, 1999, 30 (2) :275-284.

[3]CHENG ZY, PENG JC, LYU YH.Research advances in effect of epithelial-mesenchymal trcmsition on liver fibrosis[J].Chin J Clin Pharmacol Ther, 2013, 18 (8) :929-936. (in Chinese) 成志云, 彭俊纯, 吕颖慧.上皮一间充质转化对肝纤维化作用的研究进展[J].中国临床药理学与治疗学, 2013, 18 (8) :929-936.

[4]FAOUZI S, LEPREUX S, BEDIN C, et al.Activation of cultured rat hepatic stellate cells by tumoral hepatocytes[J].Lab Invest, 1999, 79 (4) :485-493.

[5]WANG W, GUAN Y, YANG ML, et al.Association between activation of hepatic stellate cells and development and metastasis of hepatocellular carcinoma[J].Chin J Clin Exp Pathol, 2007, 23 (4) :492-494. (in Chinese) 王伟, 官阳, 杨木兰, 等.活化肝星状细胞与肝细胞肝癌发生及转移的相关性[J].临床与实验病理学杂志, 2007, 23 (4) :492-494.

[6]XIA Y, CHEN R, SONG Z, et al.Gene expression profiles during activation of cultured rat hepatic stellate cells by tumoral hepatocytes and fetal bovine serum[J].J Cancer Res Clin Oncol, 2010, 136 (2) :309-321.

[7]SANCHO-BRU P, JUEZ E, MORENO M, et al.Hepatocarcinoma cells stimulate the growth, migration and expression of pro-angiogenic genes in human hepatic stellate cells[J].Liver Int, 2010, 30 (1) :31-41.

[8]ENZAN H, HIMENO H, IWAMURA S, et al.Alpha-smooth muscle actin-positive perisinusoidal stromal cells in human hepatocellular carcinoma[J].Hepatology, 1994, 19 (4) :895-903.

[9]ZHOU L, WANG Z, GAO Y, et al.Stimulation of hepatoma cell invasiveness and metastatic potential by proteins secreted from irradiated nonparenchymal cells[J].Int J Radiat Oncol Biol Phys, 2012, 84 (3) :822-828.

[10]AMANN T, BATAILLE F, SPRUSS T, et al.Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma[J].Cancer Sci, 2009, 100 (4) :646-653.

[11]ZHAO W, ZHANG L, YIN Z, et al.Activated hepatic stellate cells promote hepatocellular carcinoma development in immunocompetent mice[J].Int J Cancer, 2011, 129 (11) :2651-2661.

[12]JIA YL, SHI L, ZHOU JN, et al.Epimorphin promotes human hepatocellular carcinoma invasion and metastasis through activation of focal adhesion kinase/extracellular signal-regulated kinase/matrix metalloproteinase-9 axis[J].Hepatology, 2011, 54 (5) :1808-1818.

[13]CAMPBELL J, HUGHES S, GILBERTSON D, et al.Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma[J].Proc Natl Acad Sci U S A, 2005, 102 (9) :3389-3394.

[14]OTRANTO M, SARRAZY V, BONTF, et al.The role of the myofibroblast in tumor stroma remodeling[J].Cell Adh Migr, 2012, 6 (3) :203-219.

[15]WANG L, PARK H, CHHIM S, et al.A novel monoclonal antibody to fibroblast growth factor 2 effectively inhibits growth of hepatocellular carcinoma xenografts[J].Mol Cancer Ther, 2012, 11 (4) :864-872.

[16]WANG ZM.The study on the role of rat hepatic stellate cells promote growth and invation of hepatocellular carcinoma and alter the tumor immune microenviroment[D].Fudan University, 2012. (in Chinese) 王志明.大鼠肝星状细胞促进肝癌生长、侵袭及调控免疫微环境的实验研究[D].复旦大学, 2012.

[17]XIA Y, CHEN R, YE S, et al.Inhibition of T-cell responses by intratumoral hepatic stellate cells contribute to migration and invasion of hepatocellular carcinoma[J].Clin Exp Metastasis, 2011, 28 (7) :661-674.

[18]OGUNWOBI O, LIU C.Therapeutic and prognostic importance of epithelial-mesenchymal transition in liver cancers:insights from experimental models[J].Crit Rev Oncol Hematol, 2012, 83 (3) :319-328.

[19]GOMIS RR, ALARCON C, NADAL C, et al.C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells[J].Cancer Cell, 2006, 10 (3) :203-214.

[20]CALVISI D, FRAU M, TOMASI M, et al.Deregulation of signalling pathways in prognostic subtypes of hepatocellular carcinoma:novel insights from interspecies comparison[J].Biochim Biophys Acta, 2012, 1826 (1) :215-237.

[21]SOHN B, PARK I, LEE J, et al.Functional switching of TGFbeta1 signaling in liver cancer via epigenetic modulation of a single CpG site in TTP promoter[J].Gastroenterology, 2010, 138 (5) :1898-1908.

[22]MIKULA M, PROELL V, FISCHER AN, et al.Activated hepatic stellate cells induce tumor progression of neoplastic hepatocytes in a TGF-beta dependent fashion[J].J Cell Physiol, 2006, 209 (2) :560-567.

[23]YAN X, CHEN Y.Smad7:not only a regulator, but also a crosstalk mediator of TGF-βsignalling[J].Biochem J, 2011, 434 (1) :1-10.

[24]KESSENBROCK K, PLAKS V, WERB Z.Matrix metalloproteinases:regulators of the tumor microenvironment[J].Cell, 2010, 141 (1) :52-67.

[25]CAPECE D, FISCHIETTI M, VERZELLA D, et al.The inflammatory microenvironment in hepatocellular carcinoma:a pivotal role for tumor-associated macrophages[J].Biomed Res Int, 2013, 2013:187204.

[26]LITTLEPAGE L, STERNLICHT M, ROUGIER N, et al.Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression[J].Cancer Res, 2010, 70 (6) :2224-2234.

[27]LI J, FAN R, ZHAO S, et al.Reactive oxygen species released from hypoxic hepatocytes regulates MMP-2 expression in hepatic stellate cells[J].Int J Mol Sci, 2011, 12 (4) :2434-2447.

[28]FORNARI F, MILAZZO M, CHIECO P, et al.In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2[J].J Pathol, 2012, 227 (3) :275-285.

[29]FU B, WU Z, QIN J.Effects of integrins on laminin chemotaxis by hepatocellular carcinoma cells[J].Mol Biol Rep, 2010, 37 (3) :1665-1670.

[30]AUMAILLEY M, BRUCKNER-TUDERMAN L, CARTER W, et al.A simplified laminin nomenclature[J].Matrix Biol, 2005, 24 (5) :326-332.

[31]SANTAMATO A, FRANSVEA E, DITURI F, et al.Hepatic stellate cells stimulate HCC cell migration via laminin-5 production[J].Clin Sci (Lond) , 2011, 121 (4) :159-168.

[32]VAN ZIJL F, ZULEHNER G, PETZ M, et al.Epithelial-mesenchymal transition in hepatocellular carcinoma[J].Future Oncol, 2009, 5 (8) :1169-1179.

[33]SU Y, SHU K, HU C, et al.Hepatic stellate cells attenuate the immune response in renal transplant recipients with chronic hepatitis[J].Transplant Proc, 2012, 44 (3) :725-729.

[34]ZHAO W, SU W, KUANG P, et al.The role of hepatic stellate cells in the regulation of T-cell function and the promotion of hepatocellular carcinoma[J].Int J Oncol, 2012, 41 (2) :457-464.

[35]CHINNADURAI R, GRAKOUI A.B7-H4 mediates inhibition of T cell responses by activated murine hepatic stellate cells[J].Hepatology, 2010, 52 (6) :2177-2185.

[36]JIANG Z, CHEN Y, FENG X, et al.Hepatic stellate cells promote immunotolerance following orthotopic liver transplantation in rats via induction of T cell apoptosis and regulation of Th2/Th3-like cell cytokine production[J].Exp Ther Med, 2013, 5 (1) :165-169.

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