肿瘤间质细胞分泌成纤维生长因子10促进结肠癌细胞侵袭  

Tumor Stromal Cells Secreting Fibroblast Growth Factor 10 Promote the Metastatic Capacity of Colon-cancer Cell

作　　者：刘淑丹[1] 陈冬梅[1] 马会明[2] 荣诗阔 刘晓明[1] 梁雪云[1] Liu Shudan;Chen Dongmei;Ma Huiming(Human Stem Cell Institute of Ningxia,Ningxia Medical University,Ningxia 750004,China)

机构地区：[1]宁夏医科大学总医院干细胞研究所,银川750004 [2]宁夏医科大学教育部生育力保持重点实验室,银川750004

出　　处：《医学研究杂志》2018年第6期52-57,共6页Journal of Medical Research

基　　金：宁夏回族自治区自然科学基金资助项目(NZ15138)

摘　　要：目的确定结肠肿瘤间质细胞的旁分泌因子FGF10对肿瘤细胞侵袭的影响。方法体外分离培养结肠肿瘤间质细胞,ELISA检测其FGF10的表达,并与结肠癌细胞系HCT116和SW480共培养。同时设添加人重组FGF10培养结肠癌细胞系作为试验对照组。Real-time-PCR检测HCT116细胞侵袭相关基因的表达变化。Western blot法检测共培养后结肠癌细胞系中上皮-间质蛋白表达变化。显微镜下计数透过Matrigel包被Transwell膜的细胞数量检测细胞的侵袭能力。结果结肠肿瘤间质细胞高表达FGF10生长因子。结肠癌细胞系HCT116和SW480与TAFs共培养系统中,HCT116和SW480细胞中Twist、Snail、Slug、ZEB1基因的表达上调,Vimentin蛋白表达上调,E-cadherin蛋白表达下降,侵袭能力较正常培养细胞显著增强。同时添加人重组FGF10培养结肠癌细胞系表现出同样的表型变化。结论肿瘤微环境中肿瘤相关间质细胞分泌的FGF10能够增强结肠肿瘤细胞的侵袭能力。Objective To investigate the function of colon tumor stromal cells secreting fibroblast growth factor 10（ FGF10） on the metastatic capacity of colon-cancer cell. Methods The tumor stromal cells were isolated from the human colon tumor tissue and co-cultured with colon-cancer cell line HCT116 or SW480 in a transwell culture system. Human recombinant FGF10 treated HCT116 or SW480 culture system was set as one of control groups. The tumor associated factors（ TAFs） secreted by colon tumor stromal cells were analyzed by ELISA. The gene expression of metastatic capacity associated factors in HCT116 cell were determined by real-time PCR.The expression of E-cadherin and vimentin proteins in colon cancer cell lines were detected by Western blot. The invasion capacity of HCT116 or SW480 cells in the co-culture system was detected by a transwell invasive assay. Results Compared with the blank control group,the FGF10 level in the tumor stromal cells culture medium was higher（ P〈0.05）. The gene expression levels of Twist,Snail,Slug,ZEB1 were increased both in HCT116 cellsand in SW480 cells,which were cocultured withthe tumor stromal cells（ P〈0.05）. Also the protein levels of Vimentin were increased in both groups,but the expression level of E-cadherin was lower in co-culture system（ P〈0.05）. All of the above results were coincide with the presence of human recombination FGF10 treated culture systems. Conclusion Our results showed that,as an inducer of an EMT phenotype in colon cancer cell,FGF10 might play a role in promoting colon cancer metastasis.

关 键 词：转移性 成纤维生长因子10 旁分泌因子 肿瘤相关成纤维细胞 结肠癌 

分 类 号：R73-37[医药卫生—肿瘤]