Abstract：
BACKGROUND: Fibroblasts are necessary to the progression of cancer. However, the role of fibroblasts in peritoneal metastasis (PM) of gastric cancer (GC) remains elusive. In this study, we would explore the role of fibroblasts mediated cell interaction in PM of GC.
METHODS: Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment.
RESULTS: CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues.
CONCLUSIONS: CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.
METHODS: Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment.
RESULTS: CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues.
CONCLUSIONS: CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.
摘要：
背景：成纤维细胞是癌症进展所必需的。然而,成纤维细胞在胃癌（GC）腹膜转移（PM）中的作用仍然难以捉摸。在这项研究中,我们将探讨成纤维细胞介导的细胞相互作用在GC的PM中的作用。
方法：使用来自公共数据库GSE183904的单细胞测序数据来探索特定的成纤维细胞簇。从PM和GC组织中提取成纤维细胞。通过Westernblot验证CXCR7的表达水平，免疫组织化学。通过体外和体内研究来研究CLDN11的作用。使用多种免疫组织化学来表征肿瘤微环境。
结果：CXCR7阳性成纤维细胞在GC的PM中显著富集。CXCR7可通过激活成纤维细胞中AKT通路促进CLDN11的表达。成纤维细胞在体外和体内通过分泌CLDN11促进GC增殖和腹膜转移。此外，结果显示,CXCR7阳性成纤维细胞与组织中M2型巨噬细胞浸润显著相关.
结论：CXCR7阳性成纤维细胞通过CLDN11在GC的PM中起重要作用。靶向CXCR7阳性成纤维细胞或CLDN11的治疗可能有助于PM治疗GC。
方法：使用来自公共数据库GSE183904的单细胞测序数据来探索特定的成纤维细胞簇。从PM和GC组织中提取成纤维细胞。通过Westernblot验证CXCR7的表达水平，免疫组织化学。通过体外和体内研究来研究CLDN11的作用。使用多种免疫组织化学来表征肿瘤微环境。
结果：CXCR7阳性成纤维细胞在GC的PM中显著富集。CXCR7可通过激活成纤维细胞中AKT通路促进CLDN11的表达。成纤维细胞在体外和体内通过分泌CLDN11促进GC增殖和腹膜转移。此外，结果显示,CXCR7阳性成纤维细胞与组织中M2型巨噬细胞浸润显著相关.
结论：CXCR7阳性成纤维细胞通过CLDN11在GC的PM中起重要作用。靶向CXCR7阳性成纤维细胞或CLDN11的治疗可能有助于PM治疗GC。
