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A new anti-cancer strategy by control ling cross talk of oral carcinoma cells with extra cellular matrix molecules

Research Project

Project/Area Number 13557157
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 病態科学系歯学(含放射線系歯学)
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 Hiroko  Niigata University, Graduate School of Medical and Dental Sciences, Assistant Professor, 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 Professor, 大学院・医歯学総合研究科, 助手 (50332648)
SUZUKI Makoto  Niigata University, Medical and Dental Hospital, Lecture, 医歯学総合病院, 講師 (50107778)
NAKAJIMA Motoo  Tsukuba Research Center of Novartis Pharma KK, Manager (research), 癌研究グループ, マネージャー (研究職)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥9,700,000 (Direct Cost: ¥9,700,000)
Keywordssquamous cell carcinoma / cell culture / suramin / DNA chip analysis / RT-PCR / integrin / extracellular matrix / microdissection / マイクロディセクション法 / ノパラン硝酸プロテオグルカン / ライソゾーム / 細胞接着 / DNAチップ法 / 抗腫瘍効果
Research Abstract

In order to study a possibility of anti-cancer effect of inhibition of oral carcinoma cells' cross talk with extracellular matrix molecules, we examined various interactions between oral carcinoma cells and stromal fibroblasts by using cell lines, such as ACC3 or ACCM cells which were derived from human adenoid cystic carcinomas, and ZK-1 or MK-1 cells, which were derived from human squamous cell carcinomas.
First of all, we examined the effect of suramin, a polysulfonated naphthylurea, on biosyntheses of extracellular matrix (ECM) molecules and their receptor integrins as well as their interaction in ACC3 cells. Suramin enhanced secretion of ECM molecules by ACC3 cells into the culture medium, and it inhibited ACC3 cells to attach in a short-term culture, that was enhanced in the presence of RGD peptides. The molecular mechanism of this phenomenon was proved by our experiments using metabolic labeling, immunoprecipitation, and immunoblotting, RT-PCR, and DNA microarrays. Suramin inhibi … More ted the biosynthesis of focal adhesion kinase (FAK) and its assembly into the cell membrane via integrins. At the same time tyrosine phosphorylation of FAK and other molecules were inhibited by suramin, although the gene expression levels for integrins and FAK were not suppressed. The results indicated that enhanced secretion of ECM molecules might result from inability of ACC3 cells to trap them on their cell surface by way of integrins, because integrins failed to be sorted and to be assembled into the cell membrane due to the absence of FAK
At the same time, the important role of extracellular matrix molecules, especially perlecan, in cellular proliferation was approved in various oral tumor or embryonal cells as well as stromal cells. Perlecan was also shown to be degraded constantly in physical conditions in oral tumor cells, which may indicate that it is metabolized by them for their growth.
Based on the data obtained in this study, it is highly suggested that oral carcinoma cells require crosstalk with extracellular matrix for their survival and that their proliferation could be suppressed by the inhibition of their recognition of extracellular, matrix. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (52 results)

All 2005 2004 2003 2002 Other

All Journal Article (36 results) Publications (16 results)

  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 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
    • Journal Title

      J Histochem Cytochem (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 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
    • 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
      2003 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
      2003 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
      2003 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(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 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 52(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 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
      2003 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
      2003 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
      2003 Final Research Report Summary
  • [Journal Article] Promoter methylation and protein expression of the E-cadherin gene in the clinicopathologic 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
      2003 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

      Niigata Dent J 34(2)

      Pages: 83-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 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
    • Journal Title

      J Oral Pathol Med 33(3)

      Pages: 177-184

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 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
    • 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
      2003 Final Research Report Summary
  • [Journal Article] パールカンは歯胚エナメル器の発育分化を制御している:過剰発現系トランスジェニックマウスによる解析2004

    • Author(s)
      依田 浩子
    • Journal Title

      歯科基礎医学会雑誌 46(5)

      Pages: 144-144

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Differential expression of extracellular matrix molecules in co-culture of squamo us cell carcinoma cells and fibroblasts.2004

    • Author(s)
      Metwaly H
    • Journal Title

      J Oral Pathol Med 33(8)

      Pages: 510-510

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 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
      2003 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
      2003 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
      2003 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
      2003 Final Research Report Summary
  • [Journal Article] Perlecan regulates the enamel organ morphogenesis2004

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

      Journal of Oral Biosciences 46(5)

      Pages: 144-144

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Differential expression of extracellular matrix molecules in co-culture of squamous cell carcinoma cells and fibroblasts2004

    • Author(s)
      Metwaly, H, Cheng J, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 33(8)

      Pages: 510-510

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 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
    • Journal Title

      Int J Cancer 106(5)

      Pages: 683-689

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion)2003

    • Author(s)
      Metwaly H
    • Journal Title

      Virchows Arch 443(1)

      Pages: 17-27

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Jaw bone remodeling at the invasion front of gingival squamous cell carcinomas2003

    • Author(s)
      Ito M
    • Journal Title

      J Oral Pathol Med 32(1)

      Pages: 10-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] パールカン遺伝子の選択的スプライシング様式 -口腔がんにおける発現制御の検討-2003

    • Author(s)
      大城 和文
    • Journal Title

      日本病理学会会誌 92(1)

      Pages: 360-360

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The basement membrane-type heparan sulfate proteoglycan (perlecan) in ameloblastomas : its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells in culture2003

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

      Virchows Arch 441(2)

      Pages: 165-173

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 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
      2003 Final Research Report Summary
  • [Journal Article] Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion)2003

    • Author(s)
      Metwaly H, Cheng J, Ida-Yonemochi H, Ohshiro K, Jen KY, Liu AR, Saku T
    • Journal Title

      Virchows Arch 443(1)

      Pages: 17-27

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Jaw bone remodeling at the invasion front of gingival squamous cell carcinomas2003

    • Author(s)
      Ito M, Izumi N, Cheng J, Sakai H, Nakajima T, Oda K, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 32(1)

      Pages: 10-17

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Alternative splicing variants of perlecan, a basement membrane type heparan sulfate proteoglycan : their pathophysiological modes of expression in human oral cancer2003

    • Author(s)
      Ohshiro K, Ohnuki N, Saku T
    • Journal Title

      Proceedings of The Japanese Society of Pathology 92(1)

      Pages: 360-360

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma2002

    • Author(s)
      Frierson Jr H
    • Journal Title

      Am J Pathol 161(10)

      Pages: 1315-1323

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Expression of adhesion molecules in O-1N, hamster squamous cell carcinoma with high potential of lymph node metastasis2002

    • Author(s)
      Oda Y
    • Journal Title

      Oral Med Pathol 7(1)

      Pages: 9-18

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma2002

    • Author(s)
      Frierson Jr H, El-Naggar AK, Welsh JB, Sapinoso LM, Su Al, Cheng J, Saku T, Moskaluk CA, Hampton GM
    • Journal Title

      American Journal of Pathology 161(10)

      Pages: 1315-1323

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The basement membrane-type heparan sulfate proteoglycan (perlecan) in ameloblastomas : its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells in culture2002

    • Author(s)
      Ida-Yonemochi H, Ikarashi T, Nagata M, Hoshina H, Takagi R, Saku T
    • Journal Title

      Virchows Arch 441(2)

      Pages: 165-173

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Expression of adhesion molecules in O-1 N, hamster squamous cell carcinoma with high potential of lymph node metastasis2002

    • Author(s)
      Oda Y, Cheng J, Nakajima T, Saku T
    • Journal Title

      Oral Medicine and Pathology 7(1)

      Pages: 9-18

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 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: "lntraepithelial 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] Syafriadi M: "Carcinoma in-situ of the oral mucosa has a definite tendency towards keratinization"Oral Med Pathol. 8(2). 43-44 (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 casas"Archivs of Pathology. (in press). (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] Suzuki K: "Hepatocyto growth factor and c-Met(HGF/c-Met) in adenoid cystic carcinoma of the human salivary gland"J Oral Pathol Med. 32(2). 84-89 (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"Vichows Archiv. 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] Ida-Yonemochi, H. et al.: "The basement membrane-type hepran sulfate proteoglycan (perlecan)in amelolastomas : its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells in culture"Virchows Archiv. DO1 10 1007. S00428-001-0556-y (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sabit, H. et al.: "Enhanced expression of basement-membrane-type heparan sulfate proteglycan in tumor fibro-myxiod stroma of intrahepatic cholangio-carcinoma"Pathology International. 51(4). 248-256 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Niimi, K., et al.: "Vascular invasion in squamous cell carcinoma of human oral mucosa"Oral Oncology. 37(6). 357-364 (2001)

    • Related Report
      2001 Annual Research Report

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

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