转化生长因子β1诱导腹膜纤维化对胃癌细胞黏附的影响  

Effect of peritoneal fibrosis induced by transforming growth factor-beta 1 on the adhesion of gastric cancer cell

作　　者：吕志栋[1] 徐惠绵[2] 王海波[1] 孔滨[1] 李建国[1] 李福年[1] 宋咏梅[3] 

机构地区：[1]青岛大学医学院附属医院乳腺外科,266003 [2]中国医科大学附属第一医院肿瘤外科 [3]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所分子肿瘤学国家重点实验室

出　　处：《中华医学杂志》2012年第24期1698-1701,共4页National Medical Journal of China

基　　金：国家自然科学基金（81071956、81071633）

摘　　要：目的观察转化生长因子-β1（TGF-β1）在腹膜纤维化中的作用及其对胃癌细胞黏附的影响。方法TGF-β1作用于人腹膜间皮细胞系HMrSV5，采用RT-PCR、Western印迹、免疫荧光检测纤维黏连蛋白、胶原ⅢmRNA及蛋白水平的表达情况，采用黏附试验观察腹膜纤维化对胃癌细胞系HGC-27、HSC-39黏附的影响。结果（1）5ng／mlTGF-β1作用间皮细胞24、48、72h诱导纤维黏连蛋白、胶原ⅢmRNA及蛋白表达，并且呈时间依赖性增加，差异均有统计学意义（均P〈0．01）。（2）HGC-27胃癌细胞对TGF-B1作用24、72h间皮细胞较对照组黏附增加率为65％±5％、124％±11％，差异均有统计学意义（均P〈0．05）；HSC-39胃癌细胞系对TGF-B1作用24、72h的问皮细胞较对照组黏附增加率为85％±9％、146％±17％，差异均有统计学意义（均P〈0．05）。（3）RGD多肽特异性阻断癌细胞与细胞外基质结合的区域后胃癌细胞系HGC-27的黏附数目低于TGF-β1组，黏附减低率为65％±8％，差异有统计学意义（P〈0．05）。结论TGF-β1能够诱导间皮细胞纤维黏连蛋白、胶原Ⅲ表达，纤维化的腹膜组织增强胃癌细胞的黏附能力，为癌细胞黏附定植提供适宜的“土壤”环境。Objective To elucidate the effect of transforming growth factor-beta 1 （ TGF-β1 ） on peritoneal fibrosis and the regulation of gastric cancer adhering to mesothelial cells. Methods The peritoneal mesothelial cell line of HMrSV5 was used to determine the role of TGF-β1 in the regulation of gastric cancer cell adhering to mesothelial cells. And the mRNA and protein expressions of collagen Ⅲ and fibronectin were detected by adhesion assay, Western blot, immunofluorescent staining and reverse transcription-polymerase chain reaction （RT-PCR）. Results （ 1 ） The treatment of 5 ng/ml TGF-β1 could induce the expressions of collagen Ⅲ and fibronectin in mesothelial cells at 24, 48 and 72 h （P 〈 0. 01 ）. （2） As compared with the controls, the percentages of adhered HGC-27 and HSC-39 gastric cancer cells significantly increased under the treatment of TGF-β1 for 24 and 72 h. The increased adhesion percentages of HGC-27 were 65% ±5% and 124% ± 11% （P 〈0. 05） while those of HSC-39 85% ±9% and 146% ± 17% respectively （ P 〈0. 05 ）. （3） Arginylglycyl-aspartic acid （RGD） （ knockdown of minimal sites for cell-binding domain of extracellular matrix） decreased the number of cancer cells adhering to mesothelial cells under the stimulation of TGF-β1. And the decreased adhesion percentage of HGC-27 was 65% ±8% （P 〈0.05）. Conclusions TGF-β1 significantly stimulates the expressions of collagen Ⅲ and fibronectin in mesothelial cells. And it is associated with the increased adhesion of gastric cancer cell and offers afavorable environment for the dissemination of gastric cancer.

关 键 词：胃肿瘤 转化生长因子Β1 纤维化 间皮细胞 

分 类 号：R735.2[医药卫生—肿瘤]