上皮间充质转化对肺鳞状细胞癌侵袭和迁移能力的影响  

Effect of epithelial- to- mesenchymal transition on the invasion and migration abilities of lung squamous cell carcinoma

作　　者：郑燕君[1] 孙保存[1,2,3] 赵秀兰[1,3] 郑旭[1] 李岩磊[1] 邱志强[2] 古强[1,3] 董学易[1,3] 张艳辉[2] 

机构地区：[1]天津医科大学病理教研室,天津市300070 [2]天津医科大学肿瘤医院病理科 [3]天津医科大学总医院病理科

出　　处：《中国肿瘤临床》2015年第5期265-270,共6页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金重点项目(编号:81230050);国家自然科学基金面上项目(编号:81173091)资助~~

摘　　要：目的:研究肺鳞状细胞癌(lung squamous cell carcinoma,LSCC)上皮间充质转化(epithelial-to-mesenchymal transition,EMT)的临床意义,并阐述EMT对肺鳞癌侵袭转移能力的影响。方法:对79例肺鳞癌组织切片进行E-cadherin、Vimentin及TGF-β1的免疫组织化学染色,分析其临床意义。将肺鳞癌细胞系SK-MES-1置于含有不同浓度转化生长因子-β1(transforming growth factor,TGF-β1)的培养基中,分别诱导培养5、10 d后,利用Western blot、RT-PCR检测E-cadherin、Vimentin的表达变化,以划痕、侵袭实验来判断不同浓度、诱导时间对SK-MES-1细胞功能的影响。结果:肺鳞癌发生淋巴转移病例中E-cadherin表达较未发生淋巴转移者低,而Vimentin表达则高于未发生淋巴转移的病例,差异具有统计学意义(P<0.05)。TGF-β1阳性表达与淋巴结转移相关,差异具有统计学意义(P<0.05)。Western blot和RT-PCR显示10 ng/m L TGF-β1诱导培养的SK-MES-1细胞中,Vimentin表达增强明显,E-cadherin表达减弱。细胞划痕和侵袭实验结果表明SK-MES-1经诱导后,迁移和体外侵袭能力增强。结论:肺鳞癌的淋巴转移与上皮间充质转化有关,TGF-β1可诱导肺鳞癌细胞发生EMT,增强其侵袭和迁移的能力。Objective： To investigate the clinical significance of epithelial-to-mesenchymal（EMT） in lung squamous cell carcinoma（LSCC） and to examine the effect of EMT on the invasive and migration abilities of LSCC. Methods： Immunohistochemical staining was performed to determine the expression of E-cadherin, Vimentin, and TGF-β1 in 79 LSCC patients, and the clinical significance was explored. SK- MES- 1 lung squamous carcinoma cells were cultured in conditioned medium containing various concentrations of transforming growth factor-β1（TGF-β1） for 5 and 10 days. The expression levels of E-cadherin and Vimentin were detected via Western blot and reverse transcription-polymerase chain reaction（RT-PCR）. With different concentrations and induction times, invasion and wound healing assays were performed to evaluate the invasion and migration abilities. Results： E-cadherin expression was significantly lower, whereas Vimentin expression was significantly higher in LSCC with lymph node metastasis than in that without noda metastasis（P0.05）. In the tissues of 79 LSCC patients, TGF-β1 expression was significantly related to lymph node metastasis（P0.05）. Western blot showed that Vimentin expression was higher, whereas E-cadherin expression was lower in TGF-β1 inducing medium with 10 ng/m L SK-MES-1 cells than in the other media. RT-PCR showed similar results. Scratch test and invasion assay both showed that treatment of cells with cytokines markedly enhanced the migration and invasion of the cells. Conclusion： Lymph node metastasis of LSCC correlates with EMT. SK-MES-1 cells undergo EMT via TGF-β1 induction, which enhances invasion and migration.

关 键 词：上皮间充质转化 肺鳞状细胞癌 TGF-Β1 侵袭 迁移 

分 类 号：R734.2[医药卫生—肿瘤]