title: IL-17 promotes tumor angiogenesis through Stat3 pathway mediated upregulation of VEGF in gastric cancer.
abstract: Gastric cancer is the world's second most common malignancy and is a major threat to global health. IL-17, a CD4 T cell-derived mediator of angiogenesis, plays a major role in stimulating angiogenesis by regulating the production of a variety of proangiogenic factors, including the vascular endothelial growth factor (VEGF). The level of VEGF expression correlates with tumor progression and metastasis in gastric cancer tissues. Abnormal activation of signal transducer and activator of transcription 3 (Stat3) rendered the tumor cells highly angiogenic, which is manifested by an increased microvascular density (MVD) and considered it as a potential molecular marker for poor prognosis in gastric cancer angiogenesis. We determined that IL-17A-induced VEGF upregulation and neovascularization through a Stat3-mediated signaling pathway and hypothesized that blocking the Stat3 activation by using JSI-124, an inhibitor of phosphorylated Stat3, could significantly reduce the VEGF expression and can thus prevent angiogenesis. We showed an inhibition of angiogenesis and tumor progression when JSI-124 was treated with IL-17A in the cells and xenografts in an animal model and suggested that targeting the Stat pathway with JSI-124 could derive an effective therapeutic target for gastric cancers and could be a promising drug in gastric cancer treatment.
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China. wuxiaoqin150126@163.com.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China.
authors.forename: Jia Nian
authors.initials: JN
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China.
authors.forename: Manpeng
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510182, China. yanghui150126@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D050796:STAT3 Transcription Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: AGS cell lines; Angiogenesis; Gastric cancer; IL-17; Immunohistochemistry; Stat3; VEGF