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2002 Fiscal Year Final Research Report Summary

Establishment and Analysis of the in vivo Human Tumor Angiogenesis Model

Research Project

Project/Area Number 12470234
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTohoku University

Principal Investigator

ISHII Seiichi  Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (60221066)

Co-Investigator(Kenkyū-buntansha) MIZOI Takayuki  Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (90271949)
SATO Yasufumi  Tohoku University Institute of Development Aging and Cancer Professor, 加齢医学研究所, 教授 (50178779)
KAMEOKA Junichi  Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (30261621)
SAITO Kazuya  Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (30343049)
Project Period (FY) 2000 – 2002
Keywordscolorectal cancer / metastasis / angiogenesis / lymphangiogenesis / VEGFR-3
Research Abstract

[Purpose] The purpose of this project was to establish and analyze the "in vivo human tumor angiogenesis model".
[Materials and Methods] Four human colorectal carcinoma (CRC) cell lines, CCL188, Colo320, MIP101 and Clone A, were orthotopically implantated in the cecum of nude. Expression of angiogenic and lymphangiogenic factors in the CRC cells were analyzed by RT-PCR, ELISA and immunohistochemistry. Tumor angiogenesis was observed by CD31 immune-staining and intravital fluorescence microscopy (IVFM) with stable GFP-transfectants of each cell line. Tumor lymphangiogenesis was also examined with anti-VEGFR3 antibody.
[Results] When inoculated into the spleens of nude mice CCL188 and CX-1 produced tumors in the liver in almost 100% of mice whereas the other two cell lines rarely formed hepatic tumors. When human CRC cells were implanted orthotopically in nude mice Matrigel-suspended cells produced local tumors with significantly higher efficacy than the cells suspended in PBS or Cellmatri … More x. Matrigel also enhanced spontaneous metastasis to the liver only by the two highly metastatic CRC cell lines. However, orthotopic implantation of CRC cells with Matrigel did not increase peritoneal metastasis. All the four CRC cell lines released VEGF with different extents while CCL188 and CX-1 did greater amount than did by MTP101 and Clone A. Anti-mouse CD31 immno-staining showed induction of tumor angiogenesis 3 days after implantation of CRC cells. The results were well compatible with the findings of tumor angiogenesis observed under the IVFM with GFP transfectants. The two highly metastatic cell lines induced higher density of microvessels than the other two cell lines did. Expressions of VEGF-C and VEGF-D in CRC cells showed correlation to lymph vessel density but did not correlate to the metastatic ability to lymph nodes.
[Conclusions] VEGF, that induces tumor angiogenesis in CRC cells, may have effects on the production of hepatic metastasis. In contrast, VEGF-C and VEGF-D, that enhance tumor lymphangiogenesis, may not decide the metastatic ability to lymph nodes. Less

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] S.Ishii, T.Mizoi, et al.: "Allelic loss of the NF1 gene in anal malignant melanoma in a patient with neurofibromatosis type 1"Int J Clin Oncol. 6. 201-204 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Harada, S.Ishii, et al.: "Introduction of anti-sense CD44S CDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colon carcinoma cells"Int J Cancer. 91. 67-75 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shang-Yin Han, S.Ishii, et al.: "Functional Evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay"Cancer Res. 60. 3147-3151 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Seiichi Ishii, Takayuki Mizoi, Kenichi Shiiba, et al: "Allelic lose of the NF1 gene in anal malignant melanoma in a patient with neurofibromatosis type 1"Int J Clin Oncol. 6. 201-204 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nobuhiko Harada, Takayuki Mizoi, Seiichi Ishii, Kenichi Shiiba, et al: "Introduction of antisense CD44S cDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colon carcinoma cells"Int J Cancer. 91. 67-75 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shang-Yin Han, Seiichi Ishii, Chikashi Ishioka, et al: "Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phophatase assay"Cancer Res. 61. 3147-3151 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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