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2006 Fiscal Year Final Research Report Summary

Gene expression profiling and corresponding sub-classification of fibroblastic cells within neoplastic and non-neoplastic diseased conditions

Research Project

Project/Area Number 17590303
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

NAKAYAMA Hirofumi  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (50253068)

Co-Investigator(Kenkyū-buntansha) YASUI Wataru  Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (40191118)
Project Period (FY) 2005 – 2006
KeywordsFibroblast / pericryptal fibroblast / subserosal fibroblast / CD34 / cytokeratin 8 / podoplanin / gene expression profile / magnetic beads
Research Abstract

The purpose of this study is gene expression profiling analysis and corresponding sub-classification of fibroblastic cells within neoplastic and non-neoplastic diseased conditions.
(1) Immunohistochemical analysis using paraffin-embedded sections and monoclonal antibodies to CD34, vimentin(vim), podoplanin/D2-40(pod), cytokeratin 8(CK8), alpha-smooth muscle actin (ASMA), and high molecular weight caldesmon (HCD) was performed in gastric and colorectal neoplastic and non-neoplastic diseases. Seven kinds of fibroblastic cells were proposed; i) CD34+vim+pod-CKS-ASMA-HCD-cells in normal tissue, ii) CD34-vim+pod+CK8-ASMA-HCD-cells in early phase of cancer invasion to submucosa, acute inflammation and recent localized circulatory disturbance, and post-irradiated tissue, iii) CD34-vim+pod+CK8-ASMA+HCD-cells in desmoplastic stroma of invasive adenocarcinomas and periglandular areas of gastrointestinal adenomas, iv) CD34-vim+pod-CK8-ASMA+HCD-cells in scar tissue, v) CD34-vim+pod+CK8+ASMA+HCD-cel … More ls seen in subserosal tissue involved by neoplastic and non-neoplastic diseases, vi) CD34-vim+pod-CK8-ASMA+HCD+ cells in normal colorectal crypts (pericryptal fibroblast), vii) CD34-vim+pod-CK8-ASMA+HCD- cells in peri-glandular areas of gastrointestinal adenomas.
(2) To confirm and/or revise the proposed subtypes of fibroblastic cells, cell isolation (fibroblastic cells, lymphocytes, etc) should be hurried from the fresh normal and diseased tissues, using cell type specific cell surface markers and magnetic beads (magnetic bead method). And then, both serial analysis of gene expression and DNA microarray analysis should be done.
(3) In performing the magnetic beads method, to choose good cell surface markers for fibroblasts is most important. Both normal fibroblasts and endothelial cells express CD34 in the cell surface, but epithelial cells, mature lymphocytes and other mesenchymal cells does not; normal fibroblast are detected by CD34 in a fraction which endothelial cells are removed by CD31 antibody.
(4) No specific cell surface markers exist for cancer-associated fibroblasts (CA-Fib). Most of the cancer-associated fibroblasts express membrane-truncated matrix metalloproteinase (MT1-MMP) in their cell membrane. Specific antibodies to MT1-MMP are suitable for CA-Fib. Less

  • Research Products

    (8 results)

All 2006 2005

All Journal Article (8 results)

  • [Journal Article] Molecular characteristics of differentiated type gastric carcinomawith distinct mucin phenotype; Li-cadherin is associated with intestinal phenotype.2006

    • Author(s)
      Motoshima J
    • Journal Title

      Pathology International 56・4

      Pages: 200-205

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lack of pericryptal fibroblastic cells adjacent to intestinal epithelial metaplastic gastric glands.2006

    • Author(s)
      Nakayama H
    • Journal Title

      Histopathology 48・5

      Pages: 610-612

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cytokeratin-positive subserosal myofibroblasts in gastroduodenal ulcer; another type of myofibroblasts.2006

    • Author(s)
      Guo L
    • Journal Title

      Histology and Histopathology 21・7

      Pages: 697-704

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular characteristics of differentiated type gastric carcinoma with distinct mucin phenotype; Li-cadherin is associated with intestinal phenotype.2006

    • Author(s)
      Motoshita J
    • Journal Title

      Pathology International 56(4)

      Pages: 200-205

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Lack of pericryptal fibroblastic cells adjacent to intestinal epithelial metaplasic gastric glands.2006

    • Author(s)
      Nakayama H
    • Journal Title

      Histopathology 48(5)

      Pages: 610-612

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cytokeratin-positive subserosal myofibroblasts in gastrointestinal ulcer; anthoer type of myofibroblasts.2006

    • Author(s)
      Guo L
    • Journal Title

      Histology and Histopathology 21(7)

      Pages: 697-704

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] DNA methylation profiles of differentiated-type gastric carcinomas with distinct mucin phenotypes.2005

    • Author(s)
      Motoshita J
    • Journal Title

      Cancer Science 96・8

      Pages: 474-479

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] DNA methylation profiles of differentiated-type gastric carcinomas with distinct mucin phenotypes.2005

    • Author(s)
      Motoshita J
    • Journal Title

      Cancer Science 96(8)

      Pages: 474-479

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

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Published: 2008-05-27  

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