期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

炎性反应微环境对结肠癌细胞上皮向间质转化的作用 被引量：4

Effects of inflammatory microenvironment on the epithelial to mesenchymal transition of colon cancer cells
原文传递
导出
摘要 目的探讨炎性反应微环境中TNF-α和TGF-β1对结肠癌细胞上皮向间质转化的作用。方法以10#g／LTGF-β1或20μg／LTNF～α或两者混合后分别作用于人结肠癌细胞系SW480细胞、HCTll6细胞和经转化生长因子G受体2（TGFBR2）干扰的SW480细胞，单纯SW480细胞和HCTll6细胞分别设为空白对照，分别于作用24、48和72h观察各组细胞形态变化。采用实时定量RT-PCR和Western印迹法检测各组上皮钙黏素、神经钙黏素和波形蛋白的表达变化。通过细胞迁移实验检测TGFBR2干扰后细胞迁移能力的变化。采用单因素方差分析进行统计学处理。结果不同时间点，TGF-β1和TNF-α分别作用于sW480细胞、HCTll6细胞和经TGFBR2干扰的SW480细胞，其细胞形态均未发生明显的变化；TGF-β1和TNF-α混合作用于以上3组细胞，其中8W480细胞和经TGFBR2干扰的SW480细胞向成纤维细胞样形态变化。与TGF-β1和TNF-α混合作用的SW480组以及SW480空白组相比，经TGFBR2干扰的sw480组中上皮钙黏素mRNA表达（0．58±0．23比0．80±O．12比0．23±0．03）明显下调，神经钙黏素tuRNA表达（1．10±0．10比0．60±0．11比1．34±0．20）显著升高，差异均有统计学意义（F=46．92、47．93，P均〈0．05），而波形蛋白mRNA表达差异无统计学意义（P〉0．05）。TGF-β1和TNF-α混合作用的HCTll6组与HcTll6空白组相比，上皮钙黏素mRNA表达（0．22±0．03比0．92±0．14）明显下调，神经钙黏素（1．40±0．05比0．46±0．02）和波形蛋白（1．60±0．12比0．78±0．11）的mRNA表达均显著升高，差异均有统计学意义（F=72．59、23．67、45．19，P均〈0．05）。各组上皮钙黏素、神经钙黏素和波形蛋白的蛋白表达与mRNA表达一致。经TGFBR2干扰的SW480组A570为102．7±8．5，TGF-β1和TNF-α混合作用的SW480组和SW480空白组分别为20．1±7．6、18．3±11．2，差异有统计学意义（F-108．92，P〈0．05）。提示TGF-β1和TNF-α共同作用于TGFBR2突变的细胞后，细胞迁移能力明显增强。结论炎性反应做环境中富集TNF-v和TGF-β1时，可能有利于结肠癌细胞的早期转移，尤其对于TGFBR2突变的结肠癌细胞。 Objective To explore the effects of tumor necrosis factor （TNF-α） and transforming growth factor β1 （TGF-β1） in the inflammatory microenvironment on the epithelial to mesenchymal transition （EMT） of colon cancer cells. Methods SW480, HCT116 and SW480 interfered with transforming growth factor beta receptor 2 （TGFBR2） cells were treated with TGF-β1 （10μg/L）, TNF-α （20 μg/L）, or a combination of both. Untreated SW480 and HCT116 cells were set as blank controls. The morphologic changes of cells of each group were observed at 24, 48 and 72 hour. The expressions ofE-cadherin, N-eadherin and vimentin of each group were detected by reverse transcription-polymerase chain reaction （RT-PCR） and Western blot. The cell migration ability of cells interfered with TGFBR2 was tested by cell migration assay. The data were analyzed by one way analysis of variance. Results There were no obvious morphologic changes in SW480 cells, HCTll6 cells and SW480 interfered with TGFBR2 at different time point. Among the three groups of cells treated with TNF-α and TGF-β1 combination, the morphologic changes to fibroblast were observed in the SW480 cells and SW480 interfered with TGFBR2. Compared with the group of SW480 cells treated with TNF-α and TGF-β1 and the group of SW480 blank controls, the expression of E-cadherin at mRNA level of the group of SW480 interfered with TGFBR2 significantly decreased （0. 58±0.23 vs 0. 80± 0. 12 vs 0. 23±0.03） and the expression of N-cadherin at mRNA level remarkably increased （1. 10±0. 10 vs 0. 60±0. 11 vs 1. 34±0.20）, the differences were statistically significant （F= 46. 92,47. 93, bofh P 〈0.05）. There was no statistically significant differences in the expression of vimintin （P〉0.05）. Compared with HCT116 blank control group, the expression of E-cadherin at mRNA level of HCTll6 treated with TNF-α and TGF-β1 combination significantly decreased （0. 92±0.14 vs 0. 22±0.03）, the expression of N-cadherin（0. 46±0.02 vs 1.40±0.05） and vimintin（0. 78±0.11 vs 1.60±0.12）at mRNA level obviously increased, and the differences were statistically significant （F=72.59, 23.67,45.19, all P〈0.05）. The expressions of E-cadherin, N-cadherin and vimintin at protein level were consistent with those at mRNA level. Cell migration assay showed the A570 of the group of SW480 interfered with TGFBR2 was 102.7±8.5, and that of the SW480 cells treated with TNF-α and TGF-β1 combination and SW480 cells blank control group were 20. 1 ± 7. 6 and 18.3 ± 11. 2, respectively, and the difference was statistically significant （F = 108.92, P〈0.05）. The ability of cell migration was significantly enhanced after treated with TNF-α and TGF-131 combination in those colon cancer ceils with TGFBR2 mutant. Conclusion The rich of TNF-α and TGF-β1 in the inflammation microenvironment may facilitate the early metastasis of colon cancer cells, especially the cells with TGFBR2 mutant.
作者 李袁飞 赵和平 朱国强 刘静 贾军梅 张革红 郭亚荣 宋彬
机构地区 山西医科大学第一医院肿瘤科 普外科 解放军第二六四医院烧伤整形科
出处 《中华消化杂志》 CAS CSCD 北大核心 2014年第3期164-169,共6页 Chinese Journal of Digestion
基金 基金项目：国家自然科学青年基金（81201956） 山西省自然科学基金（2013011043-5） 高校优秀科技创新基金（C01201013）
关键词 结肠肿瘤 上皮向间质转化 转化生长因子Β1 肿瘤坏死因子Α Colonic neoplasms Epithelial to mesenchymal transition Transforming growth factorbeta1 Tumor necrosis factor-alpha
分类号 R735.35 [医药卫生—肿瘤]
  • 相关文献

参考文献15

  • 1Candido J, Hagemann T. Cancer related inflammalion [J]. J Clin Immunol, 2013,33 Suppl 1 :S79-84.
  • 2Thiery JP. Epithelial-mesenchymal transitions in tumour progression[J]. Nat Rev Cancer, 2002,2(6) :442-454.
  • 3Wu Y, Zhou BP. TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion[J]. Br J Cancer, 2010, 102(4) :639-644.
  • 4李袁飞,赵和平,刘静,朱国强,张革红,贾军梅,杨文慧.在结肠癌细胞中RNA干扰TGFBR2慢病毒载体的构建及其功能的初步研究[J].中国生物工程杂志,2013,33(5):28-34. 被引量：1
  • 5Gao D, Vahdat LT, Wong S, et al. Microenvironmental regulation of epithelial-mesenchymal transitions in cancer[J]. Cancer Res, 2012,72(19) :4883-4889.
  • 6Chen XF, Zhang HJ, Wang HB, et al. Transforming growth factor-β1 induces epithelial-to-mesenchymal transition in human lung cancer ceils via PI3K/Akt and MEK/Erkl/2 signaling pathways[J]. Mol Biol Rep, 2012, 39(4):3549- 3556.
  • 7Maier HJ, Schmidt-Strassburger U, Huber MA, et al. NF-kappaB promotes epit helial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells[J]. Cancer Lett, 2010,295(2) :214-228.
  • 8Giampieri S, Manning C, Hooper S, et al. Localized and reversible TGFheta signalling switches breast cancer ceils from cohesive to single cell motility[J]. Nat Cell BioI, 2009, 11(11) :1287-1296.
  • 9Chuang MJ, Sun KH, Tang SJ, et al. Tumor-derived tumor necrosis factor-alpha promotes progression and epithelial- mesenchymal transition in renal cell carcinoma cells[J]. Cancer Sci, 2008,99(5) :905-913.
  • 10Yamauchi Y, Kohyama T, Takizawa H,et al. Tumor necrosis factor-alpha enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-betal[J]. Exp Lung Res, 2010,36(1) : 12-24.

二级参考文献10

  • 1Morris S M, Baek J Y, Koszarek A, et al. Transforming growth factor-beta signaling promotes hepatocarcinogenesis induced by p53 loss. Hepatology, 2012,55(1 ) :121-131.
  • 2Fang W B, Jokar I, Chytil A, et al. Loss of one Tgtbr2 allele in f/broblasts promotes metastasis in MMTV: polyoma middle T transgenic and transplant mouse models of mammary tumor progression. Clinical & Experimental Metastasis, 2011,28 ( 4 ) : 351-366.
  • 3Munoz N M, Upton M, Rojas A, et al. Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation. Cancer Research, 2006,66 (20) :9837-9844.
  • 4Blobe G C, Schiemann W P, Lodish H F. Role of transforminggrowth factor beta in human disease. The New England Journal of Medicine, 2000,342 ( 18 ) : 1350-1358.
  • 5Fang W, Li X, Jiang Q, et al. Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. Journal of Translational Medicine, 2008,6 : 32.
  • 6Novitskiy S V, Pickup M W, Gorska A E, et al. TGF-beta receptor II loss promotes mammary carcinoma progression by Thl7 dependent mechanisms. Cancer Discovery, 2011, 1 ( 5 ) : 430- 441.
  • 7Pino M S, Kikuchi H, Zeng M, et al. Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability. Gastroenterology, 2010,138 (4) : 1406-1417.
  • 8Borthwick L A, Gardner A, De Soyza A, et al. Transforming growth factor-betal ( TGF-betal ) driven epithelial to mesenchymal transition (EMT) is accentuated by tumour necrosis factor alpha (TNFalpha) via crosstalk between the SMAD and NF-kappaB pathways. Cancer Microenviron, 2011,5 ( 1 ) :45-57.
  • 9Thiery J P, Sleeman J P. Complex networks orchestrate epithelial- mesenchymal transitions. Nat Rev Mol Cell Biol, 2006,7 (2): 131-142.
  • 10Fuxe J, Karlsson M C. TGF-beta-induced epithelial-mesenchymal transition: a link between cancer and inflammation. Seminars in Cancer Biology, 2012,22 (5-6) :455-461.

同被引文献91

  • 1丁维俊,张天娥,王宇,骆永珍.仙鹤草抗癌活性成分及机理探讨[J].辽宁中医杂志,2006,33(2):251-252. 被引量：38
  • 2Johansen J S, Hcyer P E, Larsen L A, et al. YKL-40 protein ex- pression in the early developing human musculoskeletal system [J]. J Histochem Cytochem,2007,55 (12) :1213 -28.
  • 3Roslind A, Balslev E, Kruse H, et al. Subcellular localization of YKL-40 in normal and malignant epithelial ceils of the breast [ J ]. Uhrastruct Patho1,2008,32 (3) : 101 - 6.
  • 4Hakala B E, White C, Recklies A D. Human cartilage gp-39, a ma- jor secretory product of articular chondrocytes and synovial ceils, is a mammalian member of a chitinase protein family [ J ]. J Biol Chem,1993, 268(34) :25803 - 10.
  • 5Johansen J S. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer [ J ]. Dan Med Bu11,2006,53(2) : 172 -209.
  • 6Hcgdall E V, Ringshoh M, Hcgdall C K, et al. YKL-40 tissue ex- pression and plasma levels in patients with ovarian cancer [ J ]. BMC Cancer, 2009, 9:8-18.
  • 7Johansen J S,Jensen B V,Roslind A,et al. Is YKL-40 a new thera- peutic target in cancer? [ J ]. Expert Opin Ther Targets,2007,11 (2) :219 -34.
  • 8Yamaguchi M, Takai S, Hosono A, et al. Bovine milk-derived ct- lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice [ J]. Biosci Biotechnol Biochem, 2014,78(4) : 672 -9.
  • 9Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011,61 ( 2 ) : 69-90.
  • 10Boyer B, Vall6s AM, Edme N. Induction and regulation of epithe- lial-mesenchymal transitions [ J ]. Bioehem Pharmacol, 2000,60 ( 8 ) : 1091 - 1099.

引证文献4

二级引证文献24

中华消化杂志
2014年 第3期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部