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The mechanisms of the highly metastatic property using human lung cancer sublines with highly metastatic potential established and the expolation of the molecular targets for lung cancer therapy

Research Project

Project/Area Number 13670620
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNippon Medical School

Principal Investigator

GEMMA Akihiko  Nippon Medical School, Medical School, Lecturer, 医学部, 講師 (20234651)

Co-Investigator(Kenkyū-buntansha) SHIBUYA Masahiko  Tokyo Metropolitan Komagome Hospital, Chief of Resp. Med, 呼吸器内科, 部長 (50142534)
KUDOH Shoji  Nippon Medical School, Medical School, Professor, 医学部, 教授 (40256912)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsLung Cancer / Metastasis / Microarray / Macroarray / Gene Expression / CDNA array / 発現プロファイル / cDNA array / expression profile / マクロアレイ / EST クローン
Research Abstract

A better understanding of the key factors of metastasis may be useful for designing new molecular targets of cancer therapy. In order to identify these factors, we established two highly metastatic human lung adenocarcinoma cell lines in an experimental metastasis model by repeated inoculation in nude mice and compared the expression profiles of two subpopulations of an adenocarcinoma cell line with high metastatic potential, with the parent cell line, using cDNA arrays; microarray and macroarray. The expression of 5 genes was found to be significantly enhanced or reduced in the highly metastatic subpopulations by microarray. One of the over-expressed genes that was identified encoded the β-galactoside-binding protein Galectin 3. A population (10/30) of the non-small-cell lung cancers examined was found to over-express the Galectin 3 gene at levels 3 times higher than normal epithelial cells. Galectin 3 may represent a novel target molecule in non-small-cell lung cancer therapy. The expression of matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor-1 (PAI-1), carcinoembryonic antigen (CEA) and etc. were upregulated or downregulated in the highly metastatic subpopulations. Altered expression of these genes seems topromote the highly metastatic phenotype in these function. To determine whether the change in p16INK4 methylation status and the genomic status of hBUB1, hMAD2, Insulin-like growth factor 2 receptor genes, chromosome 8p and 3p occurs during metastasis of primary lung cancers, we also analyzed the primary and metastatic tumor tissues and normal lung samples from 30 cases of advanced lung cancer with distant metastasis. The results of this study indicate that tumor cells in which the p16INK4 gene has been inactivated by hypermethylation of the promoter region could have an advantage in metastasis in non-small cell lung cancers. We will evaluate the clinical significance of MMP-2, PAI-1, CEA, Galectin 3 and identified unknown clones.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] AKINOBU YOSHIMURA: "Increased expression of the LGALS3 (Galectin 3) gene in human non-small cell lung cancer"Genes Chromosomeg and Cancer.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seike M.: "The promoter region of the human BUBR1 gene and its expression analysis in lung cancer"Lung Cancer. 38(3). 229-234 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gemma A: "Genomic Structure of the Human MAD2 Gene and Mutation Analysis in Human Lung and Breast Cancers"Lung Cancer. 32(3). 289-295 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kurimoto F: "Unchanged frequency of loss of heterozygosity and size of the deleted region of 8p21-23 during metastasis of lung"Int.J.of Molecular Medicine. 8(1). 89-93 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gemma A: "Alterod expression of many genes playing specific roles accumulates in highly metestatic subpopulations of a human pulmonary adenocarinoma cell"Eur J Cancer. 37. 1554-1561 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uematsu K: "Aberrations in the Gragile histidine triad(FH1T) gene in idiopathic pulmonary fibrosis"Cancer Research. 61(23). 8527-8533 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 弦間昭彦: "Annual Review 呼吸器"中外医学社. 6 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akinobu Yoshimura: "Increased expression of the LGALS3 (Gatectin 3) gene in human non-small cell lung cancer."Genes Chromosomes Cancer. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seike M: "The promoter region of the human BUBR1 gene and its expression analysis in lung cancer."Lung Cancer.. 38(3). 229-234 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gemma, A.: "Genomic Structure of the Human MAD2 Gene and Mutation Analysis in Human Lung and Breast Cancers."Lung Cancer.. 32(3). 289-295 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kurimoto, F.: "Unchanged frequency of loss of heterozygosity and size of the deleted region at 8p21-23 during metastasis of lung cancer."Int. J of Molecular Medicine. 8(1). 89-93 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gemma, A.: "Altered expression of many genes playing specific roles accumulates in highly metastatic subpopulations of a human pulmonary adenocarcinoma cell line."Eur J of Cancer. 37. 1554-1561 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uematsu, K.: "Aberrations in the fragile histidine triad (FHIT) gene in idiopathic pulmonary fibrosis."Cancer Research. 61(23). 8527-8533 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seike M: "The promoter region of the human BUBRI gene and its expression analysis in lung cancer"Lung Cancer. 38(3). 229-234 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshimura A: "Incroased expression of the LGALS3 (Galectin3) gene in human non-small cell lung cancer"Genes Chromosomes and Cancer. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Gemma A.: "Genomic Structure of the Human MAD2 Gene and Mutation Analysis in Human Lung and Breast Cancers"Lung Cancer. 32(3). 289-295 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurimoto F.: "Unchanged frequency of loss of heterozygosity and size of the deleted region at 8p21-23 during metastasis of long Cancer"International Journal of Molecular Medicine. 8(1). 89-93 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gemma A.: "Altered expression of many genes playing specific roles accumulates in highly metastatic subpopulations of a human pulmonary adeno(arc)mng cell lines"European Journal of Cancer. 37. 1554-1561 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uematsu K.: "Aberrations in the fragile histidine triad (FHIT) gene in idiopathic pulmonary fibrosis"Cancer Research. 61(23). 8527-8533 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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