Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism.
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.
Chen
Yanling
Y
Hepatobiliary Surgery Institute, Union Hospital, Fujian Medical University, Fuzhou, 350001, China.
Jiang
Lei
L
She
Feifei
F
Tang
Nanhong
N
Wang
Xiaoqian
X
Li
Xiujin
X
Han
Shenghua
S
Zhu
Jinhai
J
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
D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3