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A new anti-cancer strategy by control ling crosstalk of oral carcinoma cells with extracellular matrix molecules

Research Project

Project/Area Number 14370581
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionNiigata University

Principal Investigator

SAKU Takashi  Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (40145264)

Co-Investigator(Kenkyū-buntansha) CHENG Jun  Niigata University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40207460)
IDA Hircko  Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
OHSHIRO Kazufumi  Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (50332648)
SUZUKI Makoto  Niigata University, Medical and Dental Hospital, lecturer, 医歯学総合病院, 講師 (50107778)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥10,600,000 (Direct Cost: ¥10,600,000)
Keywordssquamous cell carcinoma / tumor stroma / co-culture / extracellular matrix / interstitial cells / in-situ hybridization / RT-PCR / microdissection / in-situハイブリダイゼーション / マイクロディセクション法 / In-situハイブリダイゼーション / 線様嚢胞癌 / 癌細胞 / リアルタイムPCR
Research Abstract

It was poorly understood which cell types, tumor cells or stromal cells, were responsible for the production of extracellular matrix (ECM) molecules in the neoplastic stroma. To investigate the role of each cell type's participation in the production of ECM molecules, as a primary experiment of this research project, the expression of four ECM molecules at the protein and the mRNA levels was studied in two kinds of co-culture systems in direct and indirect contacts between squamous cell carcinoma (SCC) cell systems and stromal fibroblast cell systems. While similar protein and mRNA expression levels for perlecan and other ECM molecules between SCC cells and fibroblasts in a monocellular culture condition, these ECM expression levels of fibroblasts were elevated, and instead those of SCC cells dropped when they were in contact with SCC cells. The differences in the levels between SCC cells and fibroblasts were significantly more evident in direct contact than in indirect contact. These results indicated that oral SCC cells produce ECM molecules in the absence of stromal fibroblasts, which correspond to carcinomas in-situ, and that they stop producing ECM in the presence of fibroblasts, which correspond to invasive SCC. These phenomena were also confirmed in tissue sections from oral carcinoma surgical specimens by immunohistochemistry and in-situ hybridization. In other experiments, ECM production and its metabolism were shown to be controlled by both parenchymal and stromal cells. It is thus suggested that stromal fibroblasts after direct contact with invading SCC cells are more responsible than SCC cells for the formation of neoplastic stroma, and that histological invasion of SCC can be defined as the presence of stromal induction. Based on the findings, we have proposed a tumor biological concept of "parenchymal-stromal switching for ECM production."

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (42 results)

All 2005 2004 2003 Other

All Journal Article (30 results) Publications (12 results)

  • [Journal Article] Extracellular matrix remodeling in oral submucous fibrosis : its stage-specific modes revealed by immunohistochemistry and in situ hybridlzation2005

    • Author(s)
      Utsunomiya H
    • Journal Title

      J Oral Pathol Med 34 (8)

      Pages: 498-507

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Establishment and characterization of new cell lines derivedfrom melanotic neuroectodermal tumor of infancy arising in the mandible2005

    • Author(s)
      Metwaly H
    • Journal Title

      Pathol lnt 55 (6)

      Pages: 331-342

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Perlecan, a basement membrane-type heparan sulfate proteoglycan, in the enamel organ : its intraepitheliallocalization in the stellate reticulum2005

    • Author(s)
      Ida-Yonemochi H
    • Journal Title

      J Histochem Cytochem 53 (6)

      Pages: 763-772

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor in salivary pleomorphic adenomas : one of the reasons for their poorly vascularized stroma2005

    • Author(s)
      Swelam W
    • Journal Title

      Virchows Archiv 446 (6)

      Pages: 653-662

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nucleotide sequences and functions of the Epstein-Barr virus latent membrane protein 1 genes isolated from salivary gland lymphoepithelial carcinomas.2005

    • Author(s)
      Jen y
    • Journal Title

      Virus Genes 30 (2)

      Pages: 223-235

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells2005

    • Author(s)
      Syafriadi M
    • Journal Title

      J Oral Pathol med 34 (3)

      Pages: 140-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiogenesis in mucous retention cyst : a human in vivo-like model of endothelial cell differentiation in mucous substrate2005

    • Author(s)
      Swelam W
    • Journal Title

      J Oral Pathol Med 34 (1)

      Pages: 30-38

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Extracellular matrix remodeling in oral submucous fibrosis : its stage-specific modes revealed by immunohistochemistry and in-situ hybridization2005

    • Author(s)
      Utsunomiya H, Tilakaratne WM, Ohshiro K, Ida-Yonemochi H, Cheng J, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 34(8)

      Pages: 498-507

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Establishment and characterization of new cell lines derived from melanotic neuroectodermal tumor of infancy arising in the mandible.2005

    • Author(s)
      Metwaly H, Cheng J, Maruyama S, Ohshiro K, Suzuki I, Hoshina Y, Saku T
    • Journal Title

      Patholgy International 55(6)

      Pages: 331-342

    • NAID

      10019345357

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Perlecan, a basement membrane type heparan sulfate proteoglycan, in the enamel organ : its intraepithelial localization in the stellate reticulum2005

    • Author(s)
      Ida-Yonemochi H, Ohshiro K, Swelam W, Metwaly H, Saku T
    • Journal Title

      Journal of Histochemistry & Cytochemistry 53(6)

      Pages: 763-772

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor in salivary pleomorphic adenomas : one of the reasons for their poorly vascularized stroma.2005

    • Author(s)
      Swelam W, Ida-Yonemochi H, Maruyama S, Ohshiro K, Cheng J, Saku T
    • Journal Title

      Virshows Arch 446(6)

      Pages: 653-662

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nucleotide sequences and functions of the epstein-barr virus latent membrane protein 1 genes isolated from salivary gland lymphoepithelial carcinomas2005

    • Author(s)
      Jen KY, Higuchi M, Cheng J, Li J, Wu LY, Li YF, Lin HL, Chen Z, Gurtsevitch V, Fujii M, Saku T
    • Journal Title

      Virus Genes 30(2)

      Pages: 223-235

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells.2005

    • Author(s)
      Syafriadi M, Cheng J, Jen KY, Ida-Yonemochi H, Suzuki M, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 34(3)

      Pages: 140-149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiogenesis in mucous retention cyst : a human in vivo-like model of endothelial cell differentiation in mucous substrate2005

    • Author(s)
      Swelam W, Ida-Yonemochi H, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 34(1)

      Pages: 30-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Extracellular matrix remodeling in oral submucous fibrosis : its stage-specific modes revealed by immunohistochemistry and in-situ hybridization2005

    • Author(s)
      Utsunomiya H
    • Journal Title

      J Oral Pathol Med (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells2005

    • Author(s)
      Syafriadi M
    • Journal Title

      J Oral Pathol Med 34(3)

      Pages: 140-149

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Establishment and characterization of new cell lines derived from melanotic neuroectodermal tumor of infancy of the mandible2005

    • Author(s)
      Metwaly H
    • Journal Title

      Pathology International (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiogenesis in mucous retention cyst : a human in vivo-like model of endothelial cell differentiation in mucous substrate2005

    • Author(s)
      Swelam W
    • Journal Title

      J Oral Pathol Med 34(1)

      Pages: 30-38

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Promoter methylation and protein expression of the E-cadherin gene in the clinic- pathologic assessment of adenoid cystic carcinoma2004

    • Author(s)
      Maruya S
    • Journal Title

      Mod Pathol 17 (6)

      Pages: 637-645

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 基底膜型へパラン硫酸プロテオグリカン・パールカンお上皮内配置 : 上皮内間質という新しい概念2004

    • Author(s)
      lda H
    • Journal Title

      新潟歯学会雑誌 34 (2)

      Pages: 83-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Basement membrane-type heparan sulfate proteoglycan (parlecan) and low-density lipoprotein (LDL) are co-localized in grnulation tissues : a possible pathogenesis of choiesterol granulomas in jaw cysts2004

    • Author(s)
      Yamazaki M
    • Journal Title

      J Oral Pathol Med 33 (3)

      Pages: 177-1884

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan rellects dysplastic changes of the oral mucosal epithelium2004

    • Author(s)
      lkarashi T
    • Journal Title

      J Oral Pathol Med 33 (2)

      Pages: 87-95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Promoter methylation and protein expression of the E-cadherin gene in the clinic-pathologic assessment of adenoid cystic carcinoma2004

    • Author(s)
      Maruya S, Urotaki H, Wada R, Saku T, Shinkawa H, Yagihashi S
    • Journal Title

      Modern Pathology 17(6)

      Pages: 637-645

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Perlecan, a basement membrane type heparan sulfate proteoglycan, in the epithelial space : a possibility is a new concept of intraepithelial stroma.2004

    • Author(s)
      Ida H, Saku T
    • Journal Title

      Niigata Dental Journal 34(2)

      Pages: 83-85

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues : a possible pathogenesis of cholesterol granulomas in jaw cysts2004

    • Author(s)
      Yamazaki M, Cheng J, Hao N, Takagi r, Jimi S, Itabe H, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 33(3)

      Pages: 177-184

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epithelium2004

    • Author(s)
      Ikarashi T, Ida-Yonemochi H, Ohshiro K, Cheng J, Saku T
    • Journal Title

      Journal of Oral pathology & Medicine 33(2)

      Pages: 87-95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 基底膜型ヘパラン硫酸プロテオグリカン・パールカンの上皮内配置:上皮内間質という新しい概念2004

    • Author(s)
      依田浩子
    • Journal Title

      新潟歯学会雑誌 34(2)

      Pages: 247-249

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Defferential expression of extracellular matrix molecules in co-culture of squamous cell carcinoma cells and fibroblasts2004

    • Author(s)
      Metwaly H
    • Journal Title

      J Oral Pathol Med 33(8)

      Pages: 510-510

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ldentification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis2003

    • Author(s)
      Nagata M
    • Journal Title

      lnt J Cancer 106 (5)

      Pages: 683-689

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis2003

    • Author(s)
      Nagata M, Fujita H, Ida H, Hoshina H, Inoue T, Seki Y, Ohnishi M, Ohyama T, Shingaki S, Kaji M, Saku T, Takagi R
    • Journal Title

      International Journal of Cancer 106(5)

      Pages: 683-689

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yamazaki M: "Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues : a possible pathogenesis of cholesterol granulomas in jaw cysts"J Oral Pathol Med. 33(4). 177-184 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikarashi T: "Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epithelium"J Oral Pathol Med. 33(2). 87-95 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Metwaly H: "Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion)"Virchows Arch. 443(1). 17-27 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jen KY: "Mutational events in LMP1 gene of Epstein-Barr virus in salivary gland lymphoepithelial carcinomas"Int J Cancer. 105(5). 654-660 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagata M: "Identification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis"Int J Cancer. 106(5). 683-689 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito M: "Jaw bone remordeling at the invasion front of gingival squamous cell carcinomas"J Oral Pathol Med. 32(1). 10-17 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saku T: "Epstein-Barr virus infected lymphepithelial carcinomas of the salivary gland in the Russia-Asian area : a clinicopathologic study of 160 cases"Arch Pathol. 47(1). 35-40 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 朔 敬: "口腔粘膜扁平上皮癌とその境界病変:組織学的評価に関する新しい動向とその病理学的背景"新潟歯学会雑誌. 32(2). 209-224 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtake S: "Precancerous foci in pleomorphic adenoma of the salivary gland : recognition of focal carcinoma and atypical tumor cells by P53 immunohistochemistry"J Oral Pathol Med. 31(10). 590-597 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ida-Yonemochi H: "The basement membrane type heparan sulfate proteoglycan (perlecan) in ameloblastomas : its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells"Virchows Arch. 441(2). 165-173 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oda Y: "Expression of adhesion molecules in O1-N, hamster squamous cell carcinoma with high potential of lymph node metastasis"Oral Med & Pathol. 7(1). 9-18 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Frierson HF: "Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma"Am J Pathol. 161(4). 1315-1323 (2002)

    • Related Report
      2002 Annual Research Report

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

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