title: Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism.
abstract: Vascular endothelial growth factor-C (VEGF-C) has a well-defined action on neoplastic lymphangiogenesis and angiogenesis through VEGF receptor-3 (VEGFR-3) and VEGFR-2, respectively, which are generally expressed in endothelial cells. The function of the VEGF-C/receptors pathway in tumor cell types is largely unknown. In this study, we examined the expression and role of VEGF-C/receptors in gallbladder cancer (GBC) cells. We examined the expression of VEGF-C in 50 surgical specimens from gallbladder cancer and three human gallbladder cancer cell lines. Both siRNA and neutralizing antibody to deplete the expression of VEGF-C were used to characterize the biological effect of VEGF-C in GBC NOZ cells. Furthermore, we examined the expression of its receptors, VEGFR-3 and VEGFR-2, in three human GBC cell lines. Our results are as follows: The expression of VEGF-C in the invasive marginal portion was significantly higher than the expression in the central portions. All the three GBC cell lines expressed VEGF-C. Treatment of NOZ cells with VEGF-C siRNA or a neutralizing antibody suppressed cell proliferation and invasion. Moreover, all the three GBC cell lines expressed VEGFR3, but only the NOZ cells expressed VEGFR-2 mRNA. Treatment of NOZ cells with a VEGFR-3 neutralizing antibody suppressed cell invasion, but treatment of NOZ cells with a VEGFR-2 neutralizing antibody suppressed cell proliferation and invasion. In conclusion, GBC cells express both VEGF-C and its receptors. VEGF-C may have a role in the progressive growth and invasion of human GBC through an autocrine mechanism.
authors: Hepatobiliary Surgery Institute, Union Hospital, Fujian Medical University, Fuzhou, 350001, China.
authors: Yanling
authors: Y
authors: Chen
authors: Lei
authors: L
authors: Jiang
authors: Feifei
authors: F
authors: She
authors: Nanhong
authors: N
authors: Tang
authors: Xiaoqian
authors: X
authors: Wang
authors: Xiujin
authors: X
authors: Li
authors: Shenghua
authors: S
authors: Han
authors: Jinhai
authors: J
authors: Zhu
mesh_terms: D019898:Autocrine Communication; D001706:Biopsy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005706:Gallbladder Neoplasms / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis* / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis* / Q000502:physiology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis* / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3