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

Shunsuke Fukumoto, Masayo Morifuji, Yoshinori Katakura, Masamichi Ohishi, Seiji Nakamura

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalClinical and Experimental Metastasis
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

Fingerprint

Endostatins
Vascular Endothelial Growth Factor C
Down-Regulation
Lymph Nodes
Neoplasm Metastasis
Neoplasms
Tongue
Nude Mice
Blood Vessels
Lymphangiogenesis
Lymphatic Vessels
Growth
Adenoviridae
Reverse Transcription
Squamous Cell Carcinoma
B-Lymphocytes
Endothelial Cells
Western Blotting
Cell Line
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells. / Fukumoto, Shunsuke; Morifuji, Masayo; Katakura, Yoshinori; Ohishi, Masamichi; Nakamura, Seiji.

In: Clinical and Experimental Metastasis, Vol. 22, No. 1, 01.01.2005, p. 31-38.

Research output: Contribution to journalArticle

@article{8576e23de1fd4f33b02ca7acc1fbbde5,
title = "Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells",
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.",
author = "Shunsuke Fukumoto and Masayo Morifuji and Yoshinori Katakura and Masamichi Ohishi and Seiji Nakamura",
year = "2005",
month = "1",
day = "1",
doi = "10.1007/s10585-005-3973-5",
language = "English",
volume = "22",
pages = "31--38",
journal = "Clinical and Experimental Metastasis",
issn = "0262-0898",
publisher = "Springer Netherlands",
number = "1",

}

TY - JOUR

T1 - Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells

AU - Fukumoto, Shunsuke

AU - Morifuji, Masayo

AU - Katakura, Yoshinori

AU - Ohishi, Masamichi

AU - Nakamura, Seiji

PY - 2005/1/1

Y1 - 2005/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=23944516519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23944516519&partnerID=8YFLogxK

U2 - 10.1007/s10585-005-3973-5

DO - 10.1007/s10585-005-3973-5

M3 - Article

C2 - 16132576

AN - SCOPUS:23944516519

VL - 22

SP - 31

EP - 38

JO - Clinical and Experimental Metastasis

JF - Clinical and Experimental Metastasis

SN - 0262-0898

IS - 1

ER -