CD44 regulates epithelial-mesenchymal transition and metastasis in nasopharyngeal cancer cells
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摘要: 目的: 研究鼻咽癌细胞中CD44与上皮-间质转化(EMT)及转移的相关性,并初步探讨CD44调控鼻咽癌细胞EMT及转移的机制。方法: Western blotting检测鼻咽癌细胞株5-8F和6-10B中CD44与EMT相关因子的表达。用带有CD44基因的质粒以脂质体瞬时转染鼻咽癌细胞株6-10B获得CD44高表达的鼻咽癌细胞。Western blotting检测转染前后细胞中CD44与EMT相关因子的表达。细胞划痕实验检测6-10B转染前后细胞迁移能力的改变。结果: 鼻咽癌细胞株5-8F中CD44和EMT相关因子基质金属蛋白酶-9(MMP-9)的表达量高于6-10B,而EMT相关因子E-钙黏蛋白的表达量低于6-10B,5-8F的迁移能力强于6-10B。CD44基因转染后的6-10B中CD44及MMP-9的表达均升高。CD44基因转染后的6-10B迁移能力明显增强。结论: 在鼻咽癌细胞中,CD44通过调控EMT进程影响鼻咽癌细胞的转移能力。Abstract: Objective: To study the correlation of CD44 with epithelial-mesenchymal transition(EMT) and metastasis in nasopharyngeal cancer cells, and explore the possible mechanism of CD44 regulates EMT and metastasis in nasopharyngeal cancer cells.Method: The CD44 and EMT-associated proteins in 5-8F and 6-10B nasopharyngeal cancer cell lines were assayed by Western blotting. The erasion trace test was performed to observe the migratory ability of 5-8F and 6-10B nasopharyngeal cancer cells. Using lipid-mediated DNA transfection technique, the low metastatic nasopharyngeal cancer cells 6-10B were transfected in vitro with plasmid which contained CD44 gene, and then new nasopharyngeal cancer cells were obtained. The CD44 and EMT-associated proteins in 6-10B, empty vector transfected and CD44-transfected cells were assayed by Western blotting. The erasion trace test was performed to observe the alteration of migratory ability of nasopharyngeal cancer cells before and after CD44 transfection.Result: The expression of CD44 and EMT-associated protein MMP-9 in 5-8F was higher than that in 6-10B, but EMT-associated protein E-Cadherin in 5-8F was lower than that in 6-10B. The migratory ability of 5-8F was higher than that of 6-10B. The expression of CD44 and MMP-9 were significantly higher in the CD44-transfected nasopharyngeal cancer cells than in the control groups. Compared with control groups, the migratory ability of CD44-transfected nasopharyngeal cancer cells was significantly increased.Conclusion: CD44 positively regulates the metastatic ability of nasopharyngeal cancer cells, which is relevant to the process of EMT.
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[1] FANG F M,CHIEN C Y,TSAI W L,et al.Quality of lifeand survival outcome for patients with nasopharyngealcarcinoma receiving three-dimensional conformal radio-therapy vs.intensity-modulated radiotherapy-a longitudi-nal study[J].Int J Radiat Oncol Biol Phys,2008,72:356-364.
[2] 赵水喜,王迎选,崔书祥,等.442例鼻咽癌放射治疗疗效观察[J].中国肿瘤临床,2004,31(10):595-596.
[3] LEE J M,DEDHAR S,KALLURI R,et al.The epitheli-al-mesenchymal transition:new insights in signaling,de-velopment,and disease[J].J Cell Biol,2006,172:973-981.
[4] NAOR D,NEDVETZKI S,GOLAN I,et al.CD44 incancer[J].Crit Rev Clin Lab Sci,2002,39:527-579.
[5] TEMPFER C,HAEUSLER G,KAIDER A,et al.Theprognostic value of CD44 isoform expression in endometri-al cancer[J].Br J Cancer,1998,77:1137-1139.
[6] TAKAHASHI S,KIMOTO N,ORITA S,et al.Relation-ship between CD44 expression and differentiation of hu-man prostate adenocarcinomas[J].Cancer Lett,1998,129:97-102.
[7] YLAGAN L R,SCHOLES J,DEMOPOULOS R.CD44:amarker of squamous differentiation in adenosquamous neo-plasms[J].Arch Pathol Lab Med,2000,124:212-215.
[8] SAUTER A,LOFT C,GRONAU S,et al.Pharmacokinet-ics,immunogenicity and safety of bivatuzumab mer-tansine,a novel CD44v6-targeting immunoconjugate,inpatients with squamous cell carcinoma of the head andneck[J].Int J Oncol,2007,30:927-935.
[9] KAWANO T,YANOMA S,NAKAMURA Y,et al.Evalu-ation of soluble adhesion molecules CD44(CD44st,CD44v5,CD44v6),ICAM-1,and VCAM-1 as tumormarkers in head and neck cancer[J].Am J Otolaryngol,2005,26:308-313.
[10] BROOKS L,NIEDOBITEK G,AGATHANGGELOU A,etal.The expression of variant CD44 in nasopharyngealcarcinoma is unrelated to expression of LMP-1[J].Am JPathol,1995,146:1102-1112.
[11] SHI Y,TIAN Y,ZHOU Y Q,et al.Inhibition of malig-nant activities of nasopharyngeal carcinoma cells withhigh expression of CD44 by siRNA[J].Oncol Rep,2007,18:397-403.
[12] SU J,XU X H,HUANG Q,et al.Identification of cancerstem-like CD44+ cells in human nasopharyngeal carci-noma cell line[J].Arch Med Res,2011,42:15-21.
[13] 王双乐,汪远仕,黄河澄,等.上皮钙粘附蛋白、黏附分子CD44H、基质金属蛋白酶-3、肿瘤转移抑制基因nm23H1和血管内皮生长因子的表达与鼻咽癌转移的关系[J].临床耳鼻咽喉科杂志,2004,18(8):470-472.
[14] THIERY J P,SLEEMAN J P.Complex networks orches-trate epithelial-mesenchymal transitions[J].Nat RevMol Cell Biol,2006,7:131-142.
[15] TSE J C,KALLURI R.Mechanisms of metastasis:epi-thelial-to-mesenchymal transition and contribution oftumor microenvironment[J].J Cell Biochem,2007,101:816-829.
[16] MANDAL M,MYERS J N,LIPPMAN S M,et al.Epithe-lial to mesenchymal transition in head and neck squa-mous carcinoma:association of Src activation with E-cadherin down-regulation,vimentin expression,and ag-gressive tumor features[J].Cancer,2008,112:2088-2100.
[17] LIN J C,LIAO S K,LEE E H,et al.Molecular eventsassociated with epithelial to mesenchymal transition ofnasopharyngeal carcinoma cells in the absence of Ep-stein-Barr virus genome[J].J Biomed Sci,2009,16:105-110.
[18] LUO Z,ZHANG L,LI Z,et al.miR-149 promotes epi-thelial-mesenchymal transition and invasion in nasopha-ryngeal carcinoma cells[J].Zhong Nan Da Xue Xue BaoYi Xue Ban,2011,36:604-609.
[19] HORIKAWA T,YOSHIZAKI T,KONDO S,et al.Ep-stein-Barr Virus latent membrane protein 1 induces snailand epithelial-mesenchymal transition in metastatic naso-pharyngeal carcinoma[J].Br J Cancer,2011,104:1160-1167.
[20] BROWN R L,REINKE L M,DAMEROW M S,et al.CD44 splice isoform switching in human and mouse epi-thelium is essential for epithelial-mesenchymal transitionand breast cancer progression[J].J Clin Invest,2011,121:1064-1074.
[21] TAKAHASHI E,NAGANO O,ISHIMOTO T,et al.Tumor necrosis factor-alpha regulates transforming growthfactor-beta-dependent epithelial-mesenchymal transitionby promoting hyaluronan-CD44-moesin interaction[J].JBiol Chem,2010,285:4060-4073.
[22] LE BRAS G F,ALLISON G L,RICHARDS N F,et al.CD44 upregulation in E-cadherin-negative esophagealcancers results in cell invasion[J].PLoS One,2011,6:e27063-e27063.
[23] PENG S T,SU C H,KUO C C,et al.CD44 crosslinking-mediated matrix metalloproteinase-9 relocation in breasttumor cells leads to enhanced metastasis[J].Int J Oncol,2007,31:1119-1126.
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