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

  • 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-β 1 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 于含有不同浓度转化生长因子- β 1(transforming growth factor,TGF-β 1)的培养基中,分别诱导培养5、10d 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-β 1 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10ng/mL TGF-β 1 诱导培养的SK-MES-1 细胞中,Vi ?mentin 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-β 1 可诱导肺鳞癌细胞发生EMT ,增强其侵袭和迁移的能力。

     

    Abstract: Objective:To investigate the clinical significance of epithelial-to-mesenchymal (EMT) in lung squamous cell carcino-ma (LSCC) and to examine the effect of EMT on the invasive and migration abilities of LSCC. Methods:Immunohistochemical stain-ing was performed to determine the expression of E-cadherin, Vimentin, and TGF- β 1 in 79LSCC 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-β 1 (TGF- β 1) for 5 and 10days. The expression levels of E-cadherin and Vimentin were detected via West-ern 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 (P <0.05). In the tissues of 79LSCC patients, TGF- β 1 expression was significantly related to lymph node metastasis ( P <0.05). Western blot showed that Vimentin expression was higher, whereas E-cadherin expression was lower in TGF-β 1 inducing medium with 10ng/mL SK-MES- 1 cells than in the other media. RT-PCR showed similar results. Scratch test and invasion assay both showed that treat -ment 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- β 1 induction, which enhances invasion and migration.

     

/

返回文章
返回