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Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism

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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.

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Acknowledgments

This study was supported by the Key Sci-Tech Research Foundation of Fujian Province in China (No.2009Y0021), and the Key Project of Fujian Medical University in China (No. 09ZD017).

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Authors and Affiliations

  1. Hepatobiliary Surgery Institute, Union Hospital, Fujian Medical University, Fuzhou, 350001, China

    Yanling Chen, Lei Jiang, Nanhong Tang, Xiaoqian Wang & Xiujin Li

  2. Department of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, Fuzhou, 350001, China

    Yanling Chen, Lei Jiang, Shenghua Han & Jinhai Zhu

  3. Research Center for Molecular Medicine, The Key Laboratory of Infection and Oncology of Universities in Fujian Province, Fujian Medical University, Fuzhou, 350004, China

    Feifei She

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  1. Yanling Chen
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  2. Lei Jiang
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Correspondence to Feifei She.

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Chen, Y., Jiang, L., She, F. et al. Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism. Mol Cell Biochem 345, 77–89 (2010). https://doi.org/10.1007/s11010-010-0562-y

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  • DOI: https://doi.org/10.1007/s11010-010-0562-y

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