Interplay of Helicobacter pylori, fibroblasts, and cancer cells induces fibroblast activation and serpin E1 expression by cancer cells to promote gastric tumorigenesis

• DOI: 10.1186/s12967-022-03537-x
• Publication Date: 2022-07-21T12:03:48Z
• Authors: Xueshu Chen; Wei Chen; Yan Zhao; Qinrong Wang; Wenling Wang; Yining Xiang; Hang Yuan; Yuan Xie; Jianjiang Zhou
• Keywords: Serpin; Cancer-Associated Fibroblasts

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