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Basic research on the growth factor and cell adhesion factor in a mechanism of invasion and metastasis of pancreatic cancer

Research Project

Project/Area Number 13470254
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

DOI Ryuichiro  Kyoto University, Surgery and Surgical Basic Science, Assistant Professor, 医学研究科, 講師 (20301236)

Co-Investigator(Kenkyū-buntansha) FUJIMOTO Koji  Kyoto University, Surgery and Surgical Basic Science, Instructor, 医学研究科, 助手 (70335280)
IMAMURA Masayuki  Kyoto University, Surgery and Surgical Basic Science, Professor, 医学研究科, 教授 (00108995)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsTGF-β / epithelial mesenchymal transition / Smad / cadherin / RhoB / 膵癌 / 浸潤 / 転移
Research Abstract

[TGF-β signal and Function of RhoB protein] We induced epithelial mesenchymal transition (EMT) in the cultured cell by TGF-β stimulation. In addition, we found the relation between EMT and invasiveness of the cells stimulated by TGF-β. We also found that the protein and mRNA expression of RhoGTPases was suppressed in TGF-β signaling. Stable clones were established by using wild-type and mutant-type of RhoB expression vectors in order to analyze RhoB protein function. We examined, in these cells, the induction of EMT, cell proliferation, anchorage-independent cell proliferation, migration and invasion. The TGF-β stimulation signal pathway is thought to be chiefly composed of Smad signal pathway and MAPKs cascade (ERK1/2, JNK/SAPK and p38MAPK). We showed that the signal pathway which related to invasion and metastasis is MAPKs cascade. [Alteration of oncogene and invasion and metastasis in pancreatic cancer] We used pancreatic cancer cell lines with the different status of K-Ras, DPC4 and to TGF-βRII gene mutation. Stable clone with DNRas was established. Stable clones with DN and CA form of RhoB, MEK1/2 and SMAD4 were also established. The ability of invasion and metastasis stimulated by TGF-β was examined by using these cells. Moreover, the state of EMT, and the expression of RhoB protein, Cdc42 and cadherin were examined in response to the TGF-β stimulation. We showed alteration of TGF-β signaling and increased invasion and metastasis by enforced activation of Ras protein. We finally confirmed alteration of K-Ras and DPC4 in pancreatic cancer tissues.

Report

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

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Masui, T.: "Expression of METH-1 and METH-2 in pancreatic cancer : Relationship with tumor invasion"Clinical Cancer Research. 7. 3437-3443 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto, Y.: "Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells"Anticancer Research. 21. 2449-2456 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hosotani, R.: "Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice"Clinical Cancer Research. 8. 1271-1276 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Lee, JU.: "Antiproliferative activity induced by the somatostatin analogue, TT-232,in human pancreatic"European Journal of Cancer. 38. 1526-1534 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masui, T.: "Expression of IL-6 receptor in pancreatic cancer : involvement in VEGF induction"Anticancer Research. 22. 4093-4100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogawa, M.: "Direct electrophilic radiofluorination of a cyclic RGD peptide for in vivo α v β3 integrin related tumor imaging"Nuclear Medicine and Biology. 30. 1-9 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawaguchi, M.: "A Novel Synthetic Arg-Gly-Asp-Containing Peptide Cyclo(-RGDf=V-) Is the Potent Inhibitor of Angiogenesis"Biochem Biophys Res Commun. 288(3). 711-717 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masui, T.: "Expression of METH-1 and METH-2 in pancreatic cancer: Relationship with tumor invasion"Clin Cancer Res. 7. 3437-3443 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto, Y.: "Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells"Anticancer Res. 21. 2449-2456 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itami, A., Imamura, M.: "Human gastrinoma cells express calcium-sensing receptor"Life Sci.. 70(2). 119-129 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hosotani, R.: "Dust-to-mucosa pancreatico-jejunostomy reduces the risk of pancreatic leakage after pancreato- duodenectomy"World J Surg. 26. 99-104 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashi, T.: "Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-I expression in pancreatic cancer"J Nucl Med. 43(2). 173-180 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hosotani, R.: "Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice"Clin Cancer Res. 8(4). 1271-1276 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hosotani, R.: "Expression of Integrin alpha Vbeta3 in Pancreatic Carcinoma: Relation to MMP-2 Activation and Lymph Node Metastasis"Pancreas. 25(2). E30-35 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Lee, JU.: "Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells"Eur J Cancer. 38(11). 1526-1534 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Doi, R.: "Surgical management of intraductal papillary mucinous tumor of the pancreas"Surgery. 132(1). 80-85 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wade, M.: "Intravenous calcium injection test is a novel complementary procedure in differential diagnosis for gastrinoma"World J Surg. Oct; 26(10). 1291-1296 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwakura, H.: "Ghrelin expression in islet cell tumors: augmented expression of ghrelin in a case of glucagonoma with multiple eodocrine neoplasm type I"J Clin Endocrinol Metab.. Nov; 87(11). 4885-4888 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masui, T.: "Expression of IL-6 receptor in pancreatic cancer: involvement in VEGF induction"Anticancer Res. 22(6C). 4093-4100 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, Y.: "High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria"Endocrine. Nov; 19(2). 127-130 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogawa, M.: "Direct electrophilic radiofluorinatiorn of a cyclic RGD peptide for in vivo αvβ3 integrin related tumor imaging"Nucl Med Biol. 30. 1-9 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tulachan, S. S.: "All-trans retinoic acid induces differentiation of ducts and endocrine cells by mesenchymal/epithelial interactions in embryonic pancreas"Diabetes. 52(1). 76-84 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komoto, I.: "Expression and Function of the Calcium-Sensing Receptor in Pancreatic Islets and Insulinoma Cells"Pancreas. Mar; 26(2). 178-184 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Doi, R.: "Carcinoma in the remnant pancreas after distal pancreatectomy for carcinoma"Eur J. Surg. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masui, T.: "RECK expression in pancreatic cancer. Its correlation with lower invasiveness and better prognosis"Clin Cancer Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuji, S.: "Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas ligand in human pancreatic adenocarcinoma"lnt J Oncol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masui, T.: "Expression of METH-1 and METH-2 in pancreatic cancer : Relationship with tumor invasion"Clinical Cancer Research. 7. 3437-3443 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyamoto, Y.: "Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells"Anticancer Research. 21. 2449-2456 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hosotani, R.: "Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice"Clinical Cancer Research. 8. 1271-1276 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lee, JU.: "Antiproliferative activily induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells"European Journal of Cancer. 38. 1526-1534 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masui, T.: "Expression of IL-6 receptor in pancreatic cancer : involvement in VEGE induction"Anticancer Research. 22. 4093-4100 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogawa, M.: "Direct electrophilic radiofluorination of a cyclic RGD peptide for in vivo α v β3 integrin related tumor imaging"Nuclear Medicine and Biology. 30. 1-9 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawaguchi, M.: "A Novel Synthetic Arg-Gly-Asp-Containing Peptide Cyclo (-RGDf=V-) is the Potent Inhibitor of Angiogenesis"Biochemical Biophysical Research Communications. 288・3. 711-717 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masui, T.: "Expression of METH-1 and METH-2 in pancreatic cancer: Relationship with tumor invasion"Clinical Cancer Research. 7・11. 3437-3443 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamoto, Y.: "Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells"Anticancer Research. 21・4. 2449-2456 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itami, A.: "Human gastrinoma cells express calcium-sensing receptor"Life Science. 70・2. 119-129 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 土井隆一郎: "膵癌の治療-現況と新しい試み-.膵癌切除術後の補助療法"外科治療. 84・6. 978-983 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 土井隆一郎: "膵癌の遺伝子治療-現状と将来の展望"外科. 63・13. 1720-1727 (2001)

    • Related Report
      2001 Annual Research Report

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

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