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2006 Fiscal Year Final Research Report Summary

Clarification of control mechanisms for lever metastasis and nerve invasion in pancreatic cancer

Research Project

Project/Area Number 17591427
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionNagoya City University

Principal Investigator

TAKAHASHI Hiroki  Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究科, 助手 (30381792)

Co-Investigator(Kenkyū-buntansha) MANABE Tadao  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院医学研究科, 教授 (80127141)
OKADA Yuji  Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院医学研究科, 講師 (10305550)
YAMAMOTO Minoru  Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究科, 助手 (70347417)
SAWAI Hirozumi  Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院医学研究科, 講師 (40336681)
Project Period (FY) 2005 – 2006
KeywordsGDNF / pancreatic cancer / transcription factor / adhesion molecule / integrin
Research Abstract

We previously reported that the neurotrophic factor GDNF has an important role in the invasive capability of pancreatic cancer cells. Furthermore, we confirmed that the integrins have a critical role for invasive and metastatic potential of pancreatic cancer cell lines. The aims of this study was to identify the role of GDNF for pancreatic cancer cell adhesive and invasive capabilities.
We report the results that we acquired till now as follows.
1. GDNF significantly activated ERK-1/2 and PI3-K signaling pathways, furthermore, the activation of transcription factor NF-kB was observed.
2. GDNF significantly enhanced the expression of integrin subunits involved in adhesive and invasive capabilities of pancreatic cancer cells.
3. GDNF correlated with the activation of ERK-1/2 signaling pathways in pancreatic cancer cells and these enhancements can be inhibited by MEK-1 inhibitor.
4. Invasive potential of pancreatic cancer cells was also regulated by NF-kB activation via GDNF stimulation. Furthermore, NF-kB inhibitor had an important role in the inhibition of neural invasion in human pancreatic cancer cells.
In this study, we proved the signaling pathways involved in neural invasion in human pancreatic cancer cells, and our results suggested that the control of these signaling pathways contributes to the improvement of cure rate for pancreatic cancer.

  • Research Products

    (44 results)

All 2007 2006 2005

All Journal Article (44 results)

  • [Journal Article] Basement membrane proteins play an important role in the invasive processes of human pancreatic cancer cells2007

    • Author(s)
      Sawai, H
    • Journal Title

      Journal of Surgical Research 139 (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immunohistochemical analysis of interleukin-1 receptor type I and α_6 integrin subunit in advanced gastrointestinal stromal tumor of the rectum with liver metastasis2007

    • Author(s)
      Sawai, H
    • Journal Title

      Hepatogastroenterology 54 (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Stem cell factor/c-kit receptor signaling enhances the proliferation and invasion of colorectal cancer cells through the PI3K/Akt pathway2007

    • Author(s)
      Yasuda, A
    • Journal Title

      Digestive Diseases and Sciences 52 (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The Relationship between GDNF and integrins in human colorectal cancer cell activity2007

    • Author(s)
      Furuta, A
    • Journal Title

      Hepatogastroenterology 54 (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synthetic Serine Protease Inhibitor, Gabexate Mesilate, Prevents Nuclear Factor-kappaB Activation and Increases TNF-alpha-Mediated Apoptosis in Human Pancreatic Cancer Cells2007

    • Author(s)
      Takahashi, H
    • Journal Title

      Digestive Diseases and Sciences 52 (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphangiogenesis2007

    • Author(s)
      Ochi, N
    • Journal Title

      Pancreas 34・4

      Pages: 444-451

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of α_6 integrin subunit is associated with malignancy in gastric gastrointestinal stromal tumors2007

    • Author(s)
      Takeyama, H
    • Journal Title

      Medical Science Monitor 13

      Pages: CR51-56

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Basement membrane proteins play an important role in the invasive processes of human pancreatic cancer cells.2007

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Journal of Surgical Research 139, (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immunohistochemical analysis of interleukin-1 receptor type I and a6 integrin subunit in advanced gastrointestinal stromal tumor of the rectum with liver metastasis2007

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Hepatogastroenterology 54, (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Stem cell factor/c-kit receptor signaling enhances the proliferation and invasion of colorectal cancer cells through the PI3K/Akt pathway2007

    • Author(s)
      Akira Yasuda
    • Journal Title

      Digestive Diseases and Sciences 52, (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The Relationship between GDNF and integrins in human colorectal cancer cell activity2007

    • Author(s)
      Akiyoshi Furuta
    • Journal Title

      Hepatogastroenterology 54, (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthetic Serine Protease Inhibitor, Gabexate Mesilate, Prevents Nuclear Factor-kappaB Activation and Increases TNF-alpha-Mediated Apoptosis in Human Pancreatic Cancer Cells2007

    • Author(s)
      Hiroki Takahashi
    • Journal Title

      Digestive Diseases and Sciences 52, (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphangiogenesis2007

    • Author(s)
      Nobuo Ochi
    • Journal Title

      Pancreas 34-4

      Pages: 444-451

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of a6 integrin subunit is associated with malignancy in gastric gastrointestinal stromal tumors2007

    • Author(s)
      Hiromitsu Takeyama
    • Journal Title

      Medical Science Monitor 13

      Pages: CR51-56

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Combined gemcitabine and alpha-interferon therapy for pancreatic cancer : Report of a case2006

    • Author(s)
      Sawai, H
    • Journal Title

      Digestive Diseases and Sciences 51

      Pages: 1285-1289

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Integrin-linked kinase activity is associated with interleukin-1α a-induced progressive behavior of pancreatic cancer and poor patient survival2006

    • Author(s)
      Sawai, H
    • Journal Title

      Oncogene 25

      Pages: 3237-3246

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of peroxisome proliferator-activated receptor-γ decreases pancreatic cancer cell invasion through modulation of the plasminogen activator system2006

    • Author(s)
      Sawai, H
    • Journal Title

      Molecular Cancer Research 4

      Pages: 159-167

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Interleukin-lα enhances the aggressive behavior of pancreatic cancer cells by regulating the α_6β_1-integrin and urokinase plasminogen activator receptor expression2006

    • Author(s)
      Sawai, H
    • Journal Title

      BMC Cell Biology 7・8

      Pages: 1-13

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinicopathological and immunohistochemical analysis of malignant features in mucinous cystic tumors of the pancreas2006

    • Author(s)
      Sawai, H
    • Journal Title

      Hepatogastroenterology 53

      Pages: 286-290

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinicopathologic study of intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas2006

    • Author(s)
      Tanaka, M
    • Journal Title

      Hepatogastroenterology 53

      Pages: 783-787

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells2006

    • Author(s)
      Yasuda, A
    • Journal Title

      Molecular Cancer 5・46

      Pages: 1-10

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Combined gemcitabine and alpha-interferon therapy for pancreatic cancer : Report of a case2006

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Digestive Diseases and Sciences 51

      Pages: 1285-1289

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Integrin-linked kinase activity is associated with interleukin-la-induced progressive behavior of pancreatic cancer and poor patient survival2006

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Oncogene 25

      Pages: 3237-3246

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of peroxisome proliferator-activated receptor-γ decreases pancreatic cancer cell invasion through modulation of the plasminogen activator system2006

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Molecular Cancer Research 4

      Pages: 159-167

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interleukin-la enhances the aggressive behavior of pancreatic cancer cells by regulating the α6β1-integrin and urokinase plasminogen activator receptor expression2006

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      BMC Cell Biology 7-8(1-13)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinicopathological and immunohistochemical analysis of malignant features in mucinous cystic tumors of the pancreas2006

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Hepatogastroenterology 53

      Pages: 286-290

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinicopathologic study of intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas2006

    • Author(s)
      Moritsugu Tanaka
    • Journal Title

      Hepatogastroenterology 53

      Pages: 783-787

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells2006

    • Author(s)
      Akira Yasuda
    • Journal Title

      Molecular Cancer 5-46

      Pages: 1-10

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The G691S RET polymorphism increases glial cell line-derived neurotrophic factor-induced pancreatic cancer cell invasion by amplifying mitogen-activated protein kinase signaling2005

    • Author(s)
      Sawai, H
    • Journal Title

      Cancer Research 65

      Pages: 11536-11544

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Anaplastic carcinoma of the pancreas with squamous features : report of a case and immunohistochemical study2005

    • Author(s)
      Sawai, H
    • Journal Title

      Medical Science Monitor 11

      Pages: CS65-68

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1/2 signaling pathway activation2005

    • Author(s)
      Sawai, H
    • Journal Title

      Molecular Cancer 4・37

      Pages: 1-12

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Interleukin-1α enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells2005

    • Author(s)
      Sawai, H
    • Journal Title

      Medical Science Monitor 11

      Pages: BR343-350

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of glial cell line-derived neurotrophic factor family members and their receptors in pancreatic cancers2005

    • Author(s)
      Ito, Y
    • Journal Title

      Surgery 138

      Pages: 788-794

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The role of Glial cell line-derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells2005

    • Author(s)
      Funahashi H
    • Journal Title

      Journal of Surgical Oncology 91

      Pages: 77-83

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Biological effect of irradiation on adhesion molecules in human colon cancer cells in vitro2005

    • Author(s)
      Hasegawa, T
    • Journal Title

      Anticancer Research 25

      Pages: 875-879

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The role of both glial cell line-derived neurotrophic factor and integrins for invasion mechanisms of pancreatic cancer2005

    • Author(s)
      Kurimoto, M
    • Journal Title

      Nagoya Medical Journal 47

      Pages: 143-154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The G691 S RET polymorphism increases glial cell line-derived neurotrophic factor-induced pancreatic cancer cell invasion by amplifying mitogen-activated protein kinase signaling2005

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Cancer research 65

      Pages: 11536-11544

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Anaplastic carcinoma of the pancreas with squamous features : report of a case and immunohistochemical study2005

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Medical Science Monitor 11

      Pages: CR65-68

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1/2 signaling pathway activation2005

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Molecular Cancer 4-37

      Pages: 1-12

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interleukin-la enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells2005

    • Author(s)
      Hirozumi Sawai
    • Journal Title

      Medical Science Monitor 11

      Pages: BR343-350

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of glial cell line-derived neurotrophic factor family members and their receptors in pancreatic cancers2005

    • Author(s)
      Yoshinori Ito
    • Journal Title

      Surgery 138

      Pages: 788-794

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The role of Glial cell line-derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells2005

    • Author(s)
      Hitoshi Funahashi
    • Journal Title

      Journal of Surgical Oncology 91

      Pages: 77-83

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Biological effect of irradiation on adhesion molecules in human colon cancer cells in vitro2005

    • Author(s)
      Takeshi Hasegawa
    • Journal Title

      Anticancer Research 25

      Pages: 875-879

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interleukin-lalpha enhances the expression of integrin integrin alphav beta3 in human pancreatic cancer cells2005

    • Author(s)
      Masaaki Kurimoto
    • Journal Title

      Nagoya Medical Journal 47

      Pages: 143-154

    • 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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