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Development of in vivo experimental system for analyses of human cancer inductive microenvironment by using NOG mice

Research Project

Project/Area Number 16300137
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionTokai University

Principal Investigator

UEYAMA Yoshito  Tokai University, School of Medicine, Professor, 医学部, 教授 (30072408)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Masato  Tokai University, School of Medicine, Professor, 医学部, 教授 (00164335)
YAMAZAKI Hitoshi  Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (20191273)
OHNISHI Yasuyuki  Central Institute for Experimental Animals, 実験動物中央研究所, 研究員 (70201382)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥5,400,000 (Direct Cost: ¥5,400,000)
KeywordsNOG mouse / Microenvironment / Angiogenesis / Metastasis / NK cell / 悪性黒色腫 / 遠隔転移抑制 / トロンボスポンジン / 間質蛋白分解酵素 / マウスモデル / ヒト癌 / ADCC / in vivo / 多発性骨髄腫
Research Abstract

We developed a reliable new experimental in vivo model system for assaying cancer inductive microenvironment by using NOD/SCID/γc^<null>(NOG) mice. Human pancreatic cancer cell lines were examined for their ability to form diverse metastatic foci in the livers of NOG mice. Using the NOG mouse model system, we established a highly metastatic cell line, liver metastasized-BxPC-3 (LM-BxPC-3). We identified forty-five genes that were either upregulated or down regulated >4-fold in the LMBxPC-3 cell line. Only S100A4 expression correlated with the ability to form liver metastases, as evaluated in our quantitative model of metastasis in NOG mice. These results suggested that new experimental systems using NOG mice gave us the reliable metastasis model to search for and develop new anti-cancer therapies and noveldrugs against this and other key molecules. We also examined the role of Thrombospondin-2 (TSP-2) on invasion and metastasis of human malignant melanoma cell line A375. We isolated three human malignant melanoma cell lines transfected with human TSP-2 (A375/TSP-2). Cellular invasive potential was evaluated using matrigel invasion / migration assay. The in vivo metastatic experiment was performed using the NOG mice in vivo experimental system, in which the tumor cells were inoculated via portal vein from the spleen. In the in vivo metastatic experiment, A375/TSP-2 showed obviously less liver metastatic foci. The weights of liver were measured as index for metastatic hepatomegary and disclosed statistically significant. The reduction of microvessel within metastatic lesions expressing TSP2 was also histologically confirmed. The results also demonstrated that the NOG mouse systems are useful to study cancer inductive microenvironments including angiogenesis or matrix protease conditions.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (15 results)

All 2006 2005 2004

All Journal Article (15 results)

  • [Journal Article] Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer2006

    • Author(s)
      Yasuhisa Oida
    • Journal Title

      Oncology Reports 16

      Pages: 457-463

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Poor outcome of patients with pulmonary adenocarcinoma showing decreased E-cadherin combined with increased S100A4 expression2006

    • Author(s)
      Noriyuki Miyazaki
    • Journal Title

      International Journal of Oncology 28

      Pages: 1369-1374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer2006

    • Author(s)
      Yasuhisa Oida et al.
    • Journal Title

      Oncology Reports 16

      Pages: 457-463

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Poor outcome of patients with pulmonary adenocarcinoma showing decreased E-cadherin combined with increased S100A4 expression2006

    • Author(s)
      Noriyuki Miyazaki et al.
    • Journal Title

      International Journal of Oncology 28

      Pages: 1369-1374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gallbladder Small Cell Carcinoma Xenograft Established by Serial Transplantation in Nude Mice2006

    • Author(s)
      Chiyoko Nishime
    • Journal Title

      Anticancer Research 26

      Pages: 79-84

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer.2006

    • Author(s)
      Yasuhisa Oida
    • Journal Title

      Oncology Reports 16

      Pages: 457-463

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The preserved expression of neuropilin(NRP) 1 contributes to a better prognosis in colon cancer2006

    • Author(s)
      Takashi Kamiya
    • Journal Title

      Oncology Reports 28

      Pages: 369-373

    • Related Report
      2006 Annual Research Report
  • [Journal Article] S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in the NOD/SCID/γc^<null>(NOG) mouse model2005

    • Author(s)
      Norihiro Ikoma
    • Journal Title

      Oncology Reports 14

      Pages: 633-637

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma2005

    • Author(s)
      Masatake Nishi
    • Journal Title

      International Journal of Oncology 26

      Pages: 1517-1524

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in the NOD/SCID/γc^<null>(NOG) mouse model2005

    • Author(s)
      Norihiro, Ikoma et al.
    • Journal Title

      Oncology Reports 14

      Pages: 633-637

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma2005

    • Author(s)
      Masatake, Nishi et al.
    • Journal Title

      International Journal of Oncology 26

      Pages: 1517-1524

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in NOD/SCID/γc^<null>(NOG) mouse model2005

    • Author(s)
      N.Ikoma, H.Yamazaki, Y.Ohnishi, Y.Ueyama, M.Nakamaura et al.
    • Journal Title

      Oncology Reports 14

      Pages: 633-637

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts2005

    • Author(s)
      A.Hamamoto, H.Yamazaki, Y.Ohnishi, Y.Ueyama, M.Nakamura et al.
    • Journal Title

      International Journal of Oncology 26

      Pages: 891-896

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Establishment of a new model of human multiple myeloma using NOD/SCID/γc^<null> (NOG) mice2004

    • Author(s)
      Yoshitaka Miyakawa
    • Journal Title

      Biochemical and Biophysical Research Communications 313

      Pages: 371-374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Establishment of a new model of human multiple myeloma using NOD/SCID/c_c^<null>(NOG)mice2004

    • Author(s)
      Y.Miyakawa, Y.Ueyama et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 11

      Pages: 258-262

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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