文献类型：期刊文献

中文题名：胃癌微环境转化后骨髓间充质干细胞的体内致瘤性

英文题名：In vivo tumorigenicity of bone marrow mesenchymal stem cells in the body after the conversion of gastric cancer microenvironment

作者：汪永锋[1];刘喜平[1];崔国宁[1];董俊刚[1];李沛清[1];明海霞[1];张炜[2]

第一作者：汪永锋

机构：[1]甘肃中医药大学基础医学院;[2]兰州大学第一附属医院

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2017

卷号：21

期号：1

起止页码：32

中文期刊名：中国组织工程研究

外文期刊名：Chinese Journal of Tissue Engineering Research

收录：CSTPCD;;北大核心:【北大核心2014】；

基金：国家自然科学基金项目(81260525)~~

语种：中文

中文关键词：干细胞;肿瘤干细胞;胃癌BCG-823细胞;骨髓间充质干细胞;共培养;胃癌微环境;胃癌干细胞;体内实验;致瘤性;抑癌基因TCF21;潜伏膜蛋白LMP1;超微结构;国家自然科学基金

外文关键词：,Bone Marrow;;Mesenchymal Stem Cells;;Stomach Neoplasms;;Tissue Engineering

摘要：背景:临床胃癌组织及裸鼠体内致瘤组织分离得到的胃癌间质干细胞,其生物学特性与骨髓间充质干细胞相似,并证明是肿瘤微环境的重要组成部分,可促进肿瘤的生长。目的:观察经胃癌微环境转化后的骨髓间充质干细胞在体内是否具有致瘤能力。方法:设立骨髓间充质干细胞单独常规培养为对照组,实验组采用Transwell小室将人胃癌BCG-823细胞与大鼠骨髓间充质干细胞非接触共培养建立胃癌微环境。收集骨髓间充质干细胞,分别在裸鼠腋下部位行皮下接种对照组细胞或实验组共培养转化后的骨髓间充质干细胞,观察裸鼠皮下有无结节形成;免疫组织化学法检测肿瘤组织潜伏膜蛋白LMP1及抑癌基因TCF21的表达;透射电镜观察肿瘤组织的超微结构。结果与结论:(1)肿瘤结节:对照组裸鼠接种单独培养的骨髓间充质干细胞7-14 d后,始终未形成肿瘤结节。实验组在第7天皮下开始出现肿瘤结节,至14 d肿瘤结节显著增大并稳定;(2)免疫组织化学显示,实验组潜伏膜蛋白LMP1呈显著现高表达状态,抑癌基因TCF21呈低表达状态;(3)透射电镜结果显示肿瘤体组织体积较大,形态不规则,细胞微绒毛异常增多,表面有许多树枝状突起,细胞内成分发生明显改变;(4)结果表明,经胃癌微环境转化的骨髓间充质干细胞具有体内致瘤能力。
BACKGROUND： The clinical gastric cancer tissues and the mesenchymal stem cells isolated from tumor tissues in the body of nude mice have similar characteristics with bone marrow mesenchymal stem cells, which are certificated to be an important part of the tumor microenvironment that can promote the growth of tumor. OBJECTIVE： To observe that whether bone marrow mesenchymal stem cells have the tumorigenic ability after the conversion of gastric microenvironment. METHODS： Bone marrow mesenchymal stem cells cultured singly and routinely were used as controls. Rat bone marrow mesenchymal stem cells were indirectly co-cultured with gastric cancer BCG-823 cells in a Transwell chamber to construct the gastric microenvironment （experimental group）. Bone marrow mesenchymal stem cells from each group were subcutaneously seeded into the forelimb armpit of nude mice, and then, the formation of subcutaneous nodules was observed. Immunohistochemical method was used to detect the expression of tumor tissue latent membrane protein 1 （LMP1） and tumor suppressor gene TCF21. Transmission electron microscope was used to observe the ultrastructure of tumor tissues. RESULTS AND CONCLUSION： After 7-14 days, there were no tumor nodules in the nude mouse armpit in the control group. On the contrary, in the experimental group, tumor nodules formed in the nude mouse armpit after 7 days, and these nodules were enlarged and kept stable until the 14th day. The immunohistochemical results showed high level of LMP1, but low level of TCF21. Under the transmission electron microscope, the tumor tissues had a large volume and an irregular shape, the cell mricovilli were increased abnormally, and there were many fendritic protrusions on the surface, indicating the presence of obvious intracellular changes. In conclusion, bone marrow mesenchymal stem cells after the conversion in the gastric microenvironment have the ability of tumorigenicity in vivo.