Dynamic changes of liver cancer stem cell markers and inflammatory factors during the induction of liver cancer in rats

doi:10.3969/j.issn.2095-4344.2015.19.009

Abstract

Abstract:

BACKGROUND: Many liver cancer stem cell markers have been found in liver cancer tissues and cell lines such as CD133, acetaldehyde dehydrogenase (ALDH), CD90, CD44, EpcAM, CD13, OV6, K19, c-kit and ABCG2. Of them, CD133, CD90 and CD44 have been shown to be strongly associated with the recurrence and metastasis of liver cancer.
OBJECTIVE: To explore the dynamic changes of liver cancer stem cell markers and inflammatory factors during the induction of liver cancer in rats and their correlation.
METHODS: Diethyl nitrosamine solution was given to Sprague-Dawley rats for 24 hours to induce rat models of liver cancer. Rats that were given common water were considered as the healthy control group.
RESULTS AND CONCLUSION: Immunohistochemical staining revealed that Kupffer cells-related ED2 expression showed a gradual increase in the model group. Compared with the healthy control group, ED2 expression was significantly higher at 12, 16, 20 and 24 weeks after induction in the model group (P < 0.05). Quantitative PCR demonstrated that CD90 showed a gradually increased trend during induction (P < 0.05). Compared with healthy tissue, CD90 increased significantly in the liver cancer tissue (P < 0.05). CD133 showed an increased trend, but one-way analysis of variance did not show significant differences (P > 0.05). During induction, no significant change was found in other liver cancer stem cell markers (P > 0.05). During the induction, tumor necrosis factor α, transforming growth factor β, MCP-1 and interleukin-6 expression levels were significantly increased (P < 0.05). Compared with healthy tissue, transforming growth factor β, MCP-1 and interleukin-6 expression levels were significantly higher in the liver cancer tissue (P < 0.05). Other inflammatory factors did not exhibit significant alterations during the induction (P > 0.05). Pearson correlation analysis demonstrated that MCP-1, transforming growth factor β and interleukin-6 expression levels were significantly positively correlated with CD90 expression (P < 0.05). These findings suggest that partial inflammatory factors released from Kupffer cells have a certain correlation with liver cancer stem cells. Kupffer cells can promote the occurrence of liver cancer.

Key words: Neoplastic Stem Cells, Liver Neoplasms, Tumor Markers, Biological

CLC Number:

R394.2

Zheng Fei, Zhou Wen-ping, Zhang Wei, Zhao Zheng-wei. Dynamic changes of liver cancer stem cell markers and inflammatory factors during the induction of liver cancer in rats [J]. Chinese Journal of Tissue Engineering Research, 2015, 19(19): 3005-3009.

Figures/Tables 1

References

[1] 陶璐,蔡捷,邝晓聪,等.肝癌耐药细胞株的建立及癌干细胞的特性[J].中国癌症防治杂志,2012,04(2):123-126.

[2] 姜姗,匡志鹏,杨帆,等.肝癌干细胞标志物CD44在化学诱癌过程中的变化及意义[J].广东医学,2013,34(10):1496-1500.

[3] 张珍妮, 匡志鹏,杨帆,等.肝癌干细胞表面标志物CK19在化学诱癌过程中的差异表达[J].肿瘤防治研究,2012,39(10):1188-1192.

[4] Bautista W, Perez-Alvarez V, Burczynski F,et al.Membrane potential differences and GABAA receptor expression in hepatic tumor and non-tumor stem cells.Can J Physiol Pharmacol. 2014;92(1):85-91.

[5] 葛彦.干细胞样脑胶质瘤细胞株的建立及CD40信号对肿瘤干细胞生物学行为的作用机制[D].苏州大学,2011.

[6] 李慧,顾健,林传明,等.脐带间充质干细胞对CIA大鼠炎症因子的干预[J].中国组织工程研究与临床康复,2011,15(36): 6701- 6704.

[7] 吴林,宦宏波,吴黎雳,等.炎症因子与肝癌干细胞标志在肝癌诱导过程中的相关性研究[J].实用临床医药杂志,2014,(7):1-6.

[8] 王光.雌激素缺乏导致的骨质疏松环境中TNF-α通过 MiR-21影响小鼠骨髓间充质干细胞成骨分化能力的研究[D].第四军医大学,2012.

[9] 韩志鹏.炎症微环境中间充质干细胞影肿瘤生长的机制研究[D].第二军医大学,2011.

[10] 陈雯,朱峰,郭光华,等.骨髓间充质干细胞对烟雾吸入性损伤兔早期炎症因子分泌的影响[J].中国危重病急救医学,2011,23(1): 21-23.

[11] 王春苗.IL-1β联合TNF-α预处理骨髓间充质干细胞促进血管细胞黏附分子-1的表达及改善缺血后心功能[D].安徽医科大学, 2014.

[12] 王春苗,王爱玲,程景林,等.TNF-α对骨髓间充质干细胞表达黏附分子及治疗心肌梗死的影响[J].安徽医科大学学报,2014,49(7): 896-900.

[13] 孙建聪.1.负载肝癌干细胞RNA树突状细胞疫苗诱导的抗肝癌免疫应答研究;2.EDIL3的表达和肝癌患者预后的关系[D].中山大学,2010.

[14] 邓小荣,李强,万红萍,等.出血性铁过载对肝癌组织中Kupffer细胞分布的影响及其意义[J].中华实验外科杂志,2012,29(10): 1921-1922.

[15] 付玉华,范丽,于丽,等.肝癌患者脂肪干细胞重编程为诱导多潜能干细胞[J].第二军医大学学报,2011,32(4):382-386.

[16] 黄艳,黄成,李俊,等.肝纤维化病程中Kupffer细胞分泌的细胞因子对肝星状细胞活化增殖、凋亡的调控[J].中国药理学通报, 2010,26(1):9-13.

[17] 陈旭征,黎金浓,胡丹,等.解毒消癥饮逆转氟尿嘧啶诱导的肝癌干细胞耐药的机制研究[J].中华细胞与干细胞杂志(电子版),2013, (4):191-196.

[18] Deng Q, Zhang Z, Feng X, et al.TRAIL-secreting mesenchymal stem cells promote apoptosis in heat-shock- treated liver cancer cells and inhibit tumor growth in nude mice. Gene Ther. 2014;21(3)317-327.

[19] Gedaly R, Galuppo R, Musgrave Y, et al. PKI-587 and sorafenib alone and in combination on inhibition of liver cancer stem cell proliferation. J Surg Res. 2013;185(1): 225-230.

[20] Zubeldia IG, Bleau AM, Redrado M,et al.Epithelial to mesenchymal transition and cancer stem cell phenotypes leading to liver metastasis are abrogated by the novel TGF beta 1-targeting peptides P17 and P144. Exp Cell Res. 2013;319(3):12-22.

[21] 刘广健,吕明德,森安史典,等.大鼠Kupffer细胞内外Sonazoid微泡超声辐照下的动态现象[J].中山大学学报(医学科学版),2012, 33(5):571-576.

[22] 朱海英,张朵,谢东甫,等.人肝癌细胞系P2-HCC的建立及体外诱导分化特性的初步研究[J].第二军医大学学报,2005,26(3): 247-250.

[23] 郑鹏翔,周欢,谭建明,等.间充质干细胞对肝癌细胞增殖、侵袭及生物学行为的影响[J].中国组织工程研究,2013,17(36): 6521-6526.

[24] 刘虹麟,许世清,彭亮,等.同一组织来源的肝癌干细胞分化能力异质性的体外研究[J].中国医药生物技术,2014,9(3):161-166.

[25] Ma S. Biology and clinical implications of CD133(+) liver cancer stem cells. Exp Cell Res. 2013;319(2): 126-132.

[26] Lan X, Wu YZ, Wang Y, et al.CD133 silencing inhibits stemness properties and enhances chemoradiosensitivity in CD133-positive liver cancer stem cells.In t J Mol Med. 2013; 31(2): 315-324.

[27] Govaert KM, Emmink BL, Nijkamp MW, et al. Hypoxia after liver surgery imposes an aggressive cancer stem cell phenotype on residual tumor cells. Ann Surg. 2014;259(4): 750-759.

[28] 韩莉,杨钦河,杨雪松,等.疏肝健脾方药对NASH大鼠Kupffer细胞NF-κB p65和IKKβ mRNA及蛋白表达的影响[J].中国病理生理杂志,2013,29(4):641-646.

[29] 张毅,宋文杰,李韧,等.MHCC97中肝癌干细胞的分离及其特性[J].中华实验外科杂志,2008,25(1):48-50.

[30] 吴盛迪,符达,刘黎黎,等.人肝癌干细胞标志物在大鼠肝癌中的表达[J].中国临床医学,2012,19(1):8-10.

[31] 陈栋,张艳,郭晖,等.RNA干扰Kupffer细胞肿瘤坏死因子-α减轻大鼠肝脏缺血再灌注损伤[J].中华肝胆外科杂志,2010,16(10): 767-769.

[32] 彭飞,余东海,王瑛,等.新生小鼠Kupffer细胞分离培养及吞噬活性测定[J].中华实验外科杂志,2014,31(6):1271-1272.

[33] 邓小荣,李强,刘峰,等.肝癌出血性铁过载微环境中Kupffer细胞的作用机制[J].中华实验外科杂志,2014,31(1):165-166.

[34] 张晓勇,周春祥.青蒿琥酯对大鼠肝Kupffer细胞分泌肝纤维化相关细胞因子的影响[J].安徽医学,2014,(10):1437-1439.

[35] 朱仁敏,张程,陈熙,等.Kupffer细胞在果糖引起的非酒精性脂肪肝中的作用[J].安徽医科大学学报,2012,47(3):257-261.

[36] Xin HW, Hari DM, Mullinax JE, et al.Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division. Stem Cells. 2012;30(4): 591-598.

[37] 陈栋,张艳,郭晖,等.RNA干扰Kupffer细胞肿瘤坏死因子-α减轻大鼠肝脏缺血再灌注损伤[J].中华肝胆外科杂志,2010,16(10): 767-769.

[38] Song YJ, Zhang SS, Guo XL, et al.Autophagy contributes to the survival of CD133+ liver cancer stem cells in the hypoxic and nutrient-deprived tumor microenvironment. Cancer Lett. 2013,339(1):70-81.

[39] 张哲,闻勤生,倪阵,等.姜黄素对脂多糖诱导大鼠肝脏Kupffer细胞NF-κB及下游炎症因子的影响[J].胃肠病学和肝病学杂志, 2013,22(10):1030-1033.

[40] 丁雄,王梦远,刘作金,等.Kupffer细胞在原发性肝细胞癌患者肝脏中的分布及意义[J].第三军医大学学报,2007,29(11): 1076-1078.

[41] 柴跃龙,龚建平,涂兵,等.参附注射液改善大鼠肝移植缺血再灌注后Kupffer细胞的激活[J].第三军医大学学报,2011,33(12): 1216-1219.

[42] 韩莉,杨钦河,张玉佩,等.疏肝健脾方药对非酒精性脂肪性肝病大鼠Kupffer细胞SREBP-1c信号通路相关基因及蛋白表达的影响[J].中成药,2014,36(5):885-892.