Background:Helicobacter pylori (H. pylori) can disrupt the tight junctions between gastric epithelial cells and penetrate the intercellular spaces acting on epithelial cells, normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs), but their interaction in gastric cancer tumorigenesis and progression remains unclear. Methods:Primary CAFs and NFs were isolated from paired gastric cancer tissues and adjacent normal tissues and identified by immunofluorescence staining and western blot analysis for FSP-1, α-SMA, FAP, and vimentin expression. RNA-sequencing was used to compare the transcriptomes between CAFs and NFs. The expressions of FAP, lumican, and α-SMA, human cytokine array, and Transwell assay were used to assess the transformation of NFs to CAFs. CCK-8 assay, colony formation, flow cytometry, Transwell assay, and nude mouse xenograft model were used to determine the effects of Serpin E1 on cell proliferation and metastasis in vitro and in vivo. Finally, Serpin E1 and/or FAP expression was measured in H. pylori-infected gerbil gastric mucosa and human gastric cancer tissues. Results:Gastric CAFs are inflammatory CAFs with α-SMAlowFAPhighlumicanhigh. The interplay of H. pylori, fibroblasts, and cancer cells promotes the transition of NFs to CAFs by inducing cytokine release, especially Serpin E1. Long-term H. pylori infection and CAFs induce Serpin E1 expression in gerbil gastric tissues and human gastric cancer cells. Serpin E1 overexpression enhances the growth, migration, invasion of gastric cancer cells in vitro, and xenograft tumor growth in nude mice via inducing angiogenesis. Serpin E1 and FAP were highly expressed in cancer cells and CAFs of gastric cancer tissues, respectively, and a good correlation was observed between their expression. Higher Serpin E1 expression is negatively associated with the overall survival of patients with gastric cancer. Conclusions:The interplay of H. pylori, fibroblasts, and cancer cells induced Serpin E1 expression to promote the activation of NFs to CAFs and gastric carcinogenesis. Targeting Serpin E1 will provide a promising therapeutic strategy for gastric cancer by disrupting the interaction between H. pylori, CAFs, and gastric cancer cells.Keywords:Fibroblasts; Gastric cancer; Helicobacter pylori; RNA-sequencing; Serpin E1.

---

 

乐备实是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。