Tiam 1与胃癌细胞侵袭转移及与裸鼠移植瘤形成的关系

Correlation of Tiam 1 to invasion and metastasis of gastric cancer cells and to development of tumor xenografts in nude mice

目的检测胃癌细胞中T淋巴瘤侵袭转移诱导因子1(Tiam 1)的表达,并分析其与胃癌细胞离体、在体侵袭转移能力的关系。方法采用层粘连蛋白黏附法,由胃癌MKN-45细胞株(M0)中筛选获得高(MH)、低(ML)黏附亚株。应用RT-PCR和定量细胞ELISA技术分别检测Tiam 1 mRNA与蛋白在M0,ML,MH细胞中的表达;应用Boyden小室法测定M0,ML,MH细胞的离体侵袭移行能力,并分析其与Tiam 1表达的关系。应用裸鼠接种法观察M0,ML,MH细胞的在体成瘤及转移能力。结果MH细胞中Tiam 1 mRNA(RV=0.855±0.051)与蛋白的表达(RD=1.262±0.165)以及其离体侵袭转移能力(24.33±8.02,52.00±14.53)、在体裸鼠肺转移率(4/5=80%)均较M0细胞(RV=0.759±0.047,RD=0.911±0.104,11.67±3.79,26.00±9.54,2/5=40%),ML细胞(RV=0.743±0.039,RD=0.892±0.101,9.67±3.06,23.67±8.50,1/5=20%)为强,统计学差异显著(P<0.05),但在M0,ML细胞间无统计学差异(P>0.05);Tiam 1表达水平与胃癌细胞的侵袭转移能力呈完全及高度正相关(P<0.05)。结论Tiam 1表达水平升高有可能促进胃癌细胞侵袭转移能力的增强。

Objective To investigate the expression of T lymphoma invasion and metastasis inducing factor 1 （ Tiam 1 ） in gastric cancer cells and analyse the correlation between Tiam 1 and the invasive and migratory potential of gastric cancer cells in vitro and in vivo. Methods Two subpopulations lesser （ ML ） and higher （MH ） adhesive subgroup were separated from human gastric cancer cell line MKN-45 （M0 ） by laminin adhesion method in vitro. RT-PCR and ELISA were applied to detect the expression of Tiam 1 mRNA and protein in M0 , ML and MH cells. The invasive and migratory potential of M0 , ML and MH cells in vitro and in vivo were observed by Boyden chamber and by inoculation into nude mice and, simultaneously, correlation between the expression of Tiam 1 and the invasive and migratory potential of gastric cancer cells was analysed. Results The invasive and migratory potential of MH cells in vitro （ 24. 33± 8.02, 52. 00 ± 14.53 ） and the lung metastatic rate of MH cells in nude-mice （4/5 = 80 % ） was much higher than that of M0 cells （11.67±3.79, 26.00±9.54, 2/5 = 40%, RV = 0.759±0.047, RD = 0.911 ± 0.104） and ML cells （9.67 ±3.06, 23.67 ±8.50, 1/5 = 20%, RV = 0.743±0.039, RD = 0.892±0. 101） （P〈 0.05）, as well as the expression of Tiam 1 mRNA （RV = 0.855±0.051） and protein （RD = 1.262 ±0. 165） in MH cells were much higher than those in MO and ML cells （P〈 0.（15） ,but there was no obvious difference between M0 and ML cells （P 〉 0. 05 ）. Positive correlation existed between the expression of Tiam 1 and the invasive and migratory potential of gastric cancer cells （ P 〈 0.05 ）. Conclusions Increasing expression of Tiam 1 may promote the invasive and migratory potential of gastric cancer cells.