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Identification of molecules responsible for invasion-independent pathway of blood-borne metastasis.

Research Project

Project/Area Number 14570126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionFukushima Medical Univerisity

Principal Investigator

SUGINO Takashi  Fukushima Medical University School of Medicine, Assistant, 医学部, 助手 (90171165)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsCancer metastasis / Invasion / Metastasis-related gene / Transfection / SLPI / Renal cell carcinoma / Hepatocellular carcinoma / Follicular thyroid carcinoma / metastasis / invasion / angiogenesis / Secretory leukocyte protease inhibitor / 肝細胞癌 / 腎細胞癌 / 血管新生 / Pleiotrophin / トランスフェクション
Research Abstract

Establishment of mouse metastatic model and identification of metastasisl-related genes : We separated sublines and clonal cell lines different in metastatic potential ; 66C8 (a non-metastatic clone), 66HM and Lu10 (highly metastatic sublines to general organs), etc from a mouse mammary tumor cell line (MCH66P) metastasizing via an invasion-independent pathway. A comparative study using these cells demonstrated that invasion-independent metastasis is related to high angiogenesis activity, especially sinusoidal development of tumor vasculature. To identify candidate genes responsible for this type of metastasis we performed differential screening using suppressive subtractive hybridization (SSH) method. Pleiotrophin, Secretory leukocyte protease inhibitor (SLPD), S3B, etc. were cloned as differentially expressed genes in higher metastatic cells among the sublines and clonal cell lines. We next transfected the candidate genes in 66C8 cells. Of five genes SLPI promoted spontaneous metastatic potential to the lung and induced sinusoidal development of tumor vessels as an index of invasion-independent metastasis.
Application of the invasion-independent metastasis model to human cancers : Histological examination using archival specimens of 10 common types of human cancers demonstrated that an invasion-independent metastatic pathway is possible in a wide variety of human cancers, especially in most cases of renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. Immunohistochemical study showed that SLPI, which promoted invasion-independent metastasis in the mouse model, was also highly expressed in real cell carcinoma.
Further studies based on these results may enable us to identify novel genes related to cancer metastasis and may present new therapeutic strategies for the amelioration of human cancers.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Takashi Sugino: "An invasion-independent pathway of blood-borne metastasis : a new murine mammary tumor model."American Journal of Pathology. 160(6). 1973-1980 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashi Sugino: "Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers."BMC Medicine. 2(1). 9 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 杉野 隆: "Invasion-independent metastasisを制御する分子の同定"乳癌基礎研究. 12. 51-54 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Aikawa: "The effect of ovariectomy and estradiol on rabbit bladder smooth muscle contraction and morphology."Journal of Urology. 170(2). 634-637 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Hashimoto: "Multiple epithelial cysts of the spleen and on the splenic capsule, and high serum levels of CA19-9, CA125 and soluble IL-2 receptor."Pathology International. 54(5). 349-354 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Hashimoto: "Liver-type fatty acid-binding protein is highly expressed in intestinat metaplasia and in a subset of carcinomas of the stomach without association with the fatty acid synthase status is the carcinoma."Pathobiology. 71(3). 115-122 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugino T.: "An invasion-independent pathway of blood-borne metastasis : a new murine mammary tumor model."Am. J. Pathol.. 160. 1973-1980 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugino T.: "Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers."BMC Med.. 2. 9 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugino T.: "Identification of genes responsible for invasion-independent metastasis."Basic Investigation of Breast Carcinoma. 12. 51-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Aikawa K.: "The effect of ovariectomy and estradiol on rabbit bladder smooth musle contraction and morphology."J Urol.. 170(2). 634-637 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hasimoto T.: "Multiple epithelial cysts of the spleen and on the splenic capsule, and high serm levels of CA19-9, CA125 and soluble IL-2 receptor."Pathol. Int.. 54(5). 349-354 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] "Liver-type fatty acid-binding protein is highly expressed in intestinal metaplasia and in a subset of carcinomas of the stomach without association with the fatty acid synthase status in the carcinoma."Pathobiol.. 71(3). 115-122 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 杉野 隆: "Invasion-independent metastasisを制御する分子の同定"乳癌基礎研究. 12. 51-54 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takashi Sugino: "Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers"BMC Medicine. 印刷中. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugino T.: "An invasion-independent pathway of blood-borne metastasis : a new murine mammary tumor model"American Journal of Pathology. 160・6. 1973-1980 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 杉野 隆: "Invasion-independent metastasisを制御する分子の同定"乳癌基礎研究. (印刷中).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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