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2001 Fiscal Year Final Research Report Summary

Analysis of micromechanisms of metastasis using NOD/SCID-hu and GFP-transfectant human colorectal carcinoma cells

Research Project

Project/Area Number 11557082
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
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) SHIIBA Kenichi  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90196345)
OTANI Haruo  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30133987)
SATO Yasufumi  Tohoku University, Research Institute of Aging and Cancer, Professor, 加齢医学研究所, 教授 (50178779)
ISHII Keiko  Tohoku University, Hospital, Lecturer, 医学部・附属病院, 講師 (00291253)
MIZOI Takayuki  Tohoku University, Hospital, Research Associate, 医学部・附属病院, 助手 (90271949)
Project Period (FY) 1999 – 2001
Keywordscolorectal cancer / metastasis / intravital microscopy / GFP / angiogenesis
Research Abstract

[Purpose] The purpose of this project was to study the micromechanisms of cancer metastasis. [Materials and Methods] Four human colorectal carcinoma (CRC) cell lines, CCL188, CX-1, MIP101 and Clone A, were used. Orthotopic implantation of CRC cells in the cecum of nude mice were carried out with the CRC cells suspeneded either n PBS, Matrigel or Cellmatrix (type I collagen). Expression of angiogenic factors in the CRC cells were analyzed by RT-PCR, ELISA and immunohistochemistry. Tumor angiogenesis was observed by CD31 immuno-staining and intravital fluorescence microscopy (IVFM) with stable GFP-transfectants of each cell line. [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 … More or Cellmatrix. 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. AH the four CRC cell lines released VEGF with different extents while CCL188 and CX-1 did greater amount than did by MIP101 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. Co-implantation of human CRC cells with normal human bone marrow cells did not induce tumor vessels of human endothelial cell origin. [Conclusions] Matrigel enhances local tumor growth and metastasis of orthotopically implanted human CRC cells in nude mice. There may be a correlation between the production of VEGF by CRC cells and the density of microvessels induced in the tumors. Less

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] S.Ishii, et al.: "Allelic loss of the NF1 gene in anal 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, et al.: "Introduction of antisense CD44S cDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasisi 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] S.Han, et al.: "Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phophatase assay"Cancer Res. 60. 3147-3151 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.M.Jessup et al.: "Carcinoembryonic antigen facilitates experimental metastasis through a mechanism that does not involve adhesion to liver cells"Clin Exp metastasis. 17. 481-488 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Seiichi Ishii, Takayuki Mizoi, Kenichi Shiiba, 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(欧文)」より
  • [Publications] Nobuhiko Harada, Takayuki Mizoi, Seiichi Ishii, Keniehi 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.. 60. 3147-3151 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.M. Jessup, Seiichi Ishii, Takayuki Mizoi, et al.: "Carcinoembryonic antigen facilitates experimental metastasis through a mechanism that does not involve adhesion to liver cells"Clin. Exp. Metastasis. 17. 481-488 (1999)

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

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Published: 2003-09-17  

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