骨髓基质干细胞（MSCs）以上皮细胞及间质细胞两种不同形式参与幽门螺杆菌（Hp）相关胃癌发生的现象尚未能得到统一解释。本课题基于我们前期MSCs表型多态性的原创发现，借用EMT/MET参与肿瘤发生发展的模型，提出MSCs表型转化（eMSCs/fMSCs）参与胃癌发生的观点。但其调控机制尚不清楚。Hp慢性感染可以导致低谷氨酰胺微环境，而近期研究显示谷氨酰胺能量代谢参与干细胞生物学调控。本课题利用干细胞能量代谢关键调控信号MAPK/ERK在eMSCs/fMSCs中差异性表达的特点，在“炎症—癌前病变—胃癌发生”不同阶段，检测Hp感染对eMSCs/fMSCs能量代谢应答影响的异同，观察eMSCs/fMSCs三羧酸循环主要代谢产物水平，下游甲基化水平，干细胞生物特性及致瘤性改变的差异，试图探讨微环境、能量代谢在差异性调控两种不同MSCs亚群参与Hp相关胃癌发生中的作用机制，为胃癌的防治提供新思路。

The mechanism underlying contribution of the bone marrow-derived mesenchymal stem cells(MSCs) to Helicobacter pylori-associated gastric cancer remains controversial, even though the concept is quite novel. Houghton et al have shown that MSCs could repopulate the gastric epithelium and progress to cancer. However, recent data has demonstrated that carcinoma associated fibroblasts (CAFs) in stomach, which promote gastric cancer progression, originated from MSCs.These clear evidences raised a model that MSCs contribute to gastric cancer as both epithelial and mesenchymal phenotype. Our previous data have investigated that MSCs present as two difference phenotypes in vitro: epithelial-like MSCs(eMSCs) and fibroblast-like MSCs(fMSCs)showing different stem cell biology, which might give an explanation for the phenotypic plasticity of MSCs in gastric cancer. However, the regulation mechanism of eMSCs/fMSCs remains unknown. The chronic H.pylori infection could lead to low glutamine microenvironment in stomach. Notably, the glutamine metabolism, mainly regulated by MAPK/ERK signal,has been recently demonstrated to be involved in the regulation of methylation status of stem cells and further effect on stem cell biology. And most interesting, MAPK/ERK signal was differentially expressed in eMSCs/fMSCs. Therefore, we address the hypothesis that the differential expressed MAPK/ERK signal in eMSCs/fMSCs could progress to gastric cancer through differential regulation of the metabolism of eMSCs/fMSCs, the aberrant methylation status of Wnt signal / promoter of Twist1, and tumorigenicity of MSCs. The project aims to emphasis the differential regulation of metabolism on eMSCs/fMSCs in different stages of inflammation, metaplasia, neoplasia and H. pylori-associated gastric cancer. To understand the real pathophysiology regulation of microenviroment, metasbolism, phenotypes diversity of MSCs (eMSCs/fMSCs) in gastric cancer holds the insightful therapeutic potential for gastric cancer patients.