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Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells

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Abstract

Anti-angiogenic therapy is a newly developed treatment method for malignant tumors. Endostatin has an anti-angiogenetic effect. Endostatin has also been shown to block the growth and metastasis of various cancers through the vascular system. However, there have so far been few reports on the relationship between endostatin and lymph node metastasis. In this study, we investigated the relationship between endostatin and the inhibition of lymph node metastasis. We first made recombinant adenovirus which expressed endostatin gene (Ad-end), and then performed the following experiments. Our findings showed Ad-end to inhibit the proliferation and tube formation of endothelial cells in vitro. In addition, Ad-end inhibited the growth of a human oral squamous cell carcinoma cell line (SQUU-B) implanted subcutaneously in the right flank of nude mice and orthotopically in the tongue of nude mice, and Ad-end also inhibited lymph node metastasis in orthotopic implantation. The number of CD31-positive blood vessels and 5’-nase-positive lymphatic vessels around Ad-end-infected tumors in tongue lesions was significantly lower than that in the control group. The down-regulation of vascular endothelial growth factor C (VEGF-C) in Ad-end-infected SQUU-B cells was recognized by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. These findings suggested that endostatin inhibited lymphangiogenesis and lymph node metastasis by suppressing the production of VEGF-C in tumor cells.

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Abbreviations

Ad-end:

recombinant adenovirus which expressed endostatin gene

bFGF:

basic fibroblast growth factor

GFP:

green fluorescent protein

MOI:

multiplicity of infection

RT-PCR:

reverse transcription-polymerase chain reaction

SCC:

squamous cell carcinoma

SQUU-B:

human oral squamous cell carcinoma cell line

VEGF:

vascular endothelial growth factor

VEGF-C:

vascular endothelial growth factor C

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Authors and Affiliations

  1. Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 1-1, Maidashi 3-chome, 812-8582, Higashi-ku, Fukuoka, Japan

    Shunsuke Fukumoto, Masayo Morifuji, Masamichi Ohishi & Seiji Nakamura

  2. Laboratory of Cellular Regulation Technology, Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan

    Yoshinori Katakura

Authors
  1. Shunsuke Fukumoto
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  2. Masayo Morifuji
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  3. Yoshinori Katakura
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  4. Masamichi Ohishi
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  5. Seiji Nakamura
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Correspondence to Shunsuke Fukumoto.

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Fukumoto, S., Morifuji, M., Katakura, Y. et al. Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells. Clin Exp Metastasis 22, 31–38 (2005). https://doi.org/10.1007/s10585-005-3973-5

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  • DOI: https://doi.org/10.1007/s10585-005-3973-5

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