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: Yanling Chen, Lei Jiang, Feifei She, Nanhong Tang, Xiaoqian Wang, Xiujin Li, Shenghua Han, Jinhai Zhu
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 345 Issue 1-2 Pg. 77-89 (Dec 2010) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 20734221 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Vascular Endothelial Growth Factor C
• Vascular Endothelial Growth Factor Receptor-2
• Vascular Endothelial Growth Factor Receptor-3

Topics

• Autocrine Communication
• Biopsy
• Cell Line, Tumor
• Cell Proliferation
• Disease Progression
• Gallbladder Neoplasms (chemistry, pathology)
• Humans
• Neoplasm Invasiveness
• RNA, Small Interfering (pharmacology)
• Vascular Endothelial Growth Factor C (analysis, physiology)
• Vascular Endothelial Growth Factor Receptor-2 (analysis, physiology)
• Vascular Endothelial Growth Factor Receptor-3 (analysis, physiology)