Jiang Chengkai, Li Yang, Li Yongsheng, Liu Liguo, Wang Xu-An, Wu Wenguang, Bao Runfa, Weng Hao, Li Maolan, Geng Yajun, Shu Yijun, Liu Yingbin
Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
State Key Laboratory for Oncogenes and Related Genes, Shanghai, 200127, China.
Med Oncol. 2022 Nov 9;40(1):10. doi: 10.1007/s12032-022-01874-x.
Fibrinogen plays an important role in tumor progression. Here, we explored the role of fibrinogen in gallbladder cancer (GBC) metastasis. The plasma fibrinogen level in M1 GBC patients was higher than in M0 GBC patients, indicating that fibrinogen may participate in GBC metastasis. Treatment of GBC cell lines with fibrinogen promoted metastasis and induced the expression of intercellular adhesion molecule 1 (ICAM1). ICAM1 overexpression promoted metastasis and knockdown inhibited it. The cell adhesion and transendothelial migration of GBC cells were enhanced by fibrinogen treatment and ICAM1 overexpression. In addition, the medium of fibrinogen-treated and overexpression-ICAM1 NOZ cells exhibited enhanced macrophages recruitment. This may work in concert to promote angiogenesis. Immunohistochemistry results on clinical specimens showed that higher fibrinogen levels, higher ICAM1 expression, higher blood vessel density, and higher macrophage levels were present simultaneously. Collectively, this study indicates fibrinogen promotes metastasis and extravasation by inducing ICAM1 expression to enhance tumor cell migration, cell adhesion, transendothelial migration and promote angiogenesis and increase vascular endothelial permeability.
纤维蛋白原在肿瘤进展中起重要作用。在此，我们探讨了纤维蛋白原在胆囊癌（GBC）转移中的作用。M1期GBC患者的血浆纤维蛋白原水平高于M0期GBC患者，这表明纤维蛋白原可能参与GBC转移。用纤维蛋白原处理GBC细胞系可促进转移并诱导细胞间黏附分子1（ICAM1）的表达。ICAM1过表达促进转移，而敲低则抑制转移。纤维蛋白原处理和ICAM1过表达增强了GBC细胞的黏附及跨内皮迁移。此外，经纤维蛋白原处理和ICAM1过表达的NOZ细胞培养基显示巨噬细胞募集增强。这可能共同作用促进血管生成。临床标本的免疫组织化学结果显示，较高的纤维蛋白原水平、较高的ICAM1表达、较高的血管密度和较高的巨噬细胞水平同时存在。总体而言，本研究表明纤维蛋白原通过诱导ICAM1表达促进转移和外渗，以增强肿瘤细胞迁移、细胞黏附、跨内皮迁移，并促进血管生成和增加血管内皮通透性。
