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Study on the genes responsible for metastasis of cancers in digestive organs and development of a novel strategy against metastasis

Research Project

Project/Area Number 07457271
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

IMAMURA Masayuki  Graduate School of Medicine, Kyoto University Professor, 医学研究科, 教授 (00108995)

Co-Investigator(Kenkyū-buntansha) ONODERA Hisashi  Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (50240825)
OHSHIO Gakuji  Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (80131100)
HOSOTANI Ryo  Graduate School of Medicine, Kyoto University Assistant Porfessor, 医学研究科, 講師 (00139908)
SHIMADA Yutaka  Graduate School of Medicine, Kyoto University Assistant Porfessor, 医学研究科, 講師 (30216072)
ARII Shigeki  Graduate School of Medicine, Kyoto University Assistant Porfessor, 医学研究科, 講師 (50151171)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥5,900,000 (Direct Cost: ¥5,900,000)
Keywordscancer of digestive organs / invasion and metastasis / gene / matrix metalloproteinase / vascular endothelial growth factor / FGF / VEGF / マトリックスメタロプロテアーゼ / Rho / Signal sequence
Research Abstract

1.Esophageal cancer
There was strong correlation between the expression of VEGF and depth of tumor, lymph node metastasis, and the microvessel count in esophageal cancer. There was also a significant correlation between the VEGF expression and the p53 mutaion. MRP1/CD9 which is a cell motility inhibiting protein was related to the depth of invasion and lymph node metastasis. However, KAI1 which is a family protein of MRP1/CD9 is reduced in most cancer cells and suggests that this protein is related to esophageal carcinogenesis. On the other hand, E-Cadherin, alpha-Catenin, and beta-Catenin have no correlation to clinico-pathological charcteristics of esophageal cancer.
2.Colon cancer
Northern blot hybridization with surgically-extirpated specimen clarified that degree of mRNA expression in VEGF,MMP-9, and MT-MMP was positively correlated with hepatic metastasis, respectively. The Patient with more than 2 highly-expressed genes in their primary lesions was found to be regarded as a high ri … More sk patient for hepatic metastasis.
3.Hepatocellular carcinoma
We reveled that MMP-9, MT-MMP and b-FGF were strongly participated in the invasion into tumor capsule which was an important phenotype representing the invasion potential of hepatocellular carcinoma.
4.Pancreas cancer
Activation of MMP and expression of VEGF were determined in surgically obtained pancreatic cancer tisuue, with the use of gelatin zymography, Western blotting or immunohistochemistry. Activited form of MMP-2 was found in all of the pancreatic cancer tissues and MMP-2 activation ratio in cancer tissue was significantly higher than those in chronic pancreatitis tissues ; meanwhile, expression of activated form of MMP-9 in pancreatic cancer tissue was low and not different from chronic pancreatitis tissue. MMP-2 activation ratio of the primary cancer tissue was significantly correlated with peripancreatic invasion of the tumor, and lymph node metastasis and liver metastasis. Expression of VEGF in pancreatic cancer tissue was seen in 70% of the tissues studied and was well correlated with the vascular density of the tumor.
5.A novel gene responsible for prognosis of patients with HCC
We discovered a gene which specifically expressed in the liver and designated as kan-1. Later on, it was identified that the gene encodes acid CoA-amino acid N-acyltransferase. We showed that kan-1 mRNA expression was adversely correlated with survival time of HCC patients, being regarded as a novel and useful predictive factor for a prognosis of HCC. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(24 results)

All Other

All Publications (24 results)

  • [Publications] M. Mise: "Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene in liver tumor" Hepatology. 23. 455-464 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S. Arii: "Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential" Hepatology. 24. 316-322 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M. Furutani: "Kan-1 (bile acid CoA amino acid N-acyltransferase) mRNA as a novel paedictive indicator for prognosis of hepatocellular carcinoma patients after partial hepatectomy" Hepatology. 24. 1441-1445 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y. Shimada: "The predictive value of monolayer culture pattering in primary cell culture in esophageal cancer" Br. J. Surg.83. 1148-1151 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H. Tanaka: "Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines : Increased frequency and different spectrum of mutations from primary tumors" Int. J. Cancer. 65. 372-376 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T. Koshiba: "Detection of matrix metalloproteinase activity in human pancreatic cancer" Surgery Today. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Mise, S.Arii, H.Higashitsuji, M.Furutani, N.Niwano, T.Harada, S.Ishigami, Y.Toda, H.Nakayama, M.Fukumoto, J.Fujita, M.Imamura: "Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor." Hepatology. 23. 455-464 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Arii, M.Mise, T.Harada, M.Furutani, S.Ishigami, M.Niwano, M.Mizumoto, M.Fukumoto, M.Imamura: "Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential" Hepatology. 24. 316-322 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Furutani, S.Arii, H.Higashitsuji, M.Mise, M.Niwano, T.Harada, H.Nakayama, M.Fukumoto, M.Imamura, J.Fujita: "Kan-1 (bile acid CoA : amino acid N-acyltransferase) mRNA as a novel predictive indicator for prognosis of hepatocellular carcinoma patients after partial hepatectomy." Hepatology. 24. 1441-1445 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Shimada, Y.Kanda, I.Shibagaki, M.Kato, G.Watanabe, H.Tanaka, M.Kano, M.Imamura.: "Prognostic value of monolayr culture patterning in primary cell culture in esophageal cancer." Br J Surg. 83. 1148-1151 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Tanaka, I.Shibagaki, Y.Shimada, T.Wagata, Imamura, K.Ishizaki.: "Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines : Increased frequency and different spectrum of mutations from primary tumors" Int J Cancer. 65. 372-376 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Koshiba, R.Hosotani, M.Wada, K.Fujimoto, J.U.Lee, R.Doi, S.Arii, M.Imamura: "Detection of matrix metalloproteinase activity in human pancreatic cancer" Surgery Today. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Mise: "Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor" Hepatology. 23. 455-464 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Arii: "Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential" Hepatology. 24. 316-322 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Furutani: "Kan-1 (bile acid CoA amino acid N-acyltransferase) mRNA as a novel paedictive indicator for prognosis of hepatocellular carcinoma patients after partial hepatectomy" Hepatology. 24. 1441-1445 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Shimada: "The predictive value of monolayer culture pattering in primary cell culture in esophageal cancer" Br J Surg. 83. 1148-1151 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka H: "Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines : Increased frequency and different spectrum of mutations from primay tumors" Int J Cancer. 65. 372-376 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koshiba Z: "Detection of matrix metalloproteinase activity in human pancreatic cancer" Surgery Today. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 嶋田裕: "食道癌の分子生物学(新外科体系追補1-消化管の外科)" 中山書店, 319 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M. Mise: "Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor" Hepatology. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Arii: "Matrix metalloproteinase 9 gene expression in the invasive potential of hepatocellular carcinoma" Hepatology. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Furutani: "Reduced expression of Kan 1. encoding pmative bile acid coA: amino acid N acyltransferase. mRNA in livers of rats after partial hepatectomy and during scpsis" Biochemical Journal. 311. 203-208 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 有井滋樹: "肝細胞癌の血管新生、被膜浸潤の分子機構" 医学のあゆみ. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] 有井滋樹: "血管新生と癌転移" 外科. (印刷中).

    • Related Report
      1995 Annual Research Report

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Published: 1995-03-31   Modified: 2016-04-21  

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