Invasive pancreatic cancer specific apoptosis induction therapy by microRNA.

• Project/Area Number: 20390202
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: SHIMOSEGAWA Toru Tohoku University, 大学院・医学系研究科, 教授 (90226275)
• Co-Investigator(Kenkyū-buntansha): SATOH Kennichi 東北大学, 病院, 講師 (10282055) ; HAMADA Shin 東北大学, 病院, 医員 (20451560)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 膵癌 / EMT / microRNA / マイクロRNA / アポトーシス

Research Abstract

We performed the comprehensive analysis of microRNA expression profile to identify novel microRNAs which regulate invasiveness of pancreatic cancer. The cluster analysis identified miR-126 as a significantly down-regulated microRNA in invasive pancreatic cancer, which attenuates migration and invasion of pancreatic cancer cells. Furthermore, ADAM9 was newly identified as a target gene of miR-126, of which knockdown resulted in the decreased migration and invasion of pancreatic cancer cells. The miR-126/ADAM9 pathway could be a novel therapeutic target of invasive pancreatic cancer.

Research Products

• [Journal Article] The homeobox gene MSX2 determines chemosensitivity of pancreatic cancer cells via the regulation of transporter gene ABCG2. (2011)
  • Author(s): Hamada S, Satoh K, Hirota M, Kanno A, Umino J, Ito H, Masamune A, Kikuta K, Kume K, Shimosegawa T.
  • Journal Title: J Cell Physiol. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Biomarkers of pancreatic cancer. (2011)
  • Author(s): Hamada S, Shimosegawa T.
  • Journal Title: Pancreatology. 11 Suppl 2 Pages: 14-19
  • Peer Reviewed
• [Journal Article] Calcium-binding protein S100P is a novel diagnostic marker of cholangiocarcinoma. (2011)
  • Author(s): Hamada S, Satoh K, Hirota M, Kanno A, Ishida K, Umino J, Ito H, Kikuta K, Kume K, Masamune A, Katayose Y, Unno M, Shimosegawa T.
  • Journal Title: Cancer Sci. 102(1) Pages: 150-156
  • NAID: 10029288859
  • Peer Reviewed
• [Journal Article] Evaluation of MSX2 mRNA in brush cytology specimens distinguished pancreatic carcinoma from chronic pancreatitis. (2011)
  • Author(s): Satoh K, Hamada S, Kanno A, Ishida K, Ito H, Hirota M, Masamune A, Egawa S, Unno M, Shimosegawa T.
  • Journal Title: Cancer Sci. 102(1) Pages: 157-161
  • NAID: 10029288885
  • Peer Reviewed
• [Journal Article] Evaluation of MSX2 mRNA in brush cytology specimens distinguished pancreatic carcinoma from chronic pancreatitis. (2011)
  • Author(s): Satoh K, Hamada S, Kanno A, Ishid a K, Ito H, Hirota M, Masamune A, Egawa S, Unno M, Shimosegawa T.
  • Journal Title: Cancer Sci. Volume: 102(1) Pages: 157-161
  • NAID: 10029288885
  • Peer Reviewed
• [Journal Article] Calcium-binding protein SlOOP is a novel diagnostic marker of cholangi ocarcinoma. (2011)
  • Author(s): Hamada 5, Satoh K, Hirota M, Kanno A, Ishida K, Umino J, Ito H, Kikuta K, Kume K, Masamune A, Kat avose Y, Unno M, Shimosegawa T.
  • Journal Title: Cancer Sci. Volume: 102(1) Pages: 150-156
  • Peer Reviewed
• [Journal Article] Prediction of invasive carcinoma in branch type intraductal papillary mucinous neoplasms of the pancreas. (2010)
  • Author(s): Kanno A, Satoh K, Hirota M, Hamada S, Umino J, Itoh H, Masamune A, Asakura T, Shimosegawa T.
  • Journal Title: J Gastroenterol. 45(9) Pages: 952-959
  • NAID: 10027699047
  • Peer Reviewed
• [Journal Article] Prediction of invasive carcinoma in branch type intraductal papillary mucinous neoplasms of the pancreas. (2010)
  • Author(s): Satoh K, Hamada S, Kanno A, Hirot a M, Umino J, Ito H, Masamune A, Egawa S, Unno M, Shimosegawa T.
  • Journal Title: IJ Gastroenterol. Volume: 45(9) Pages: 952-959
  • NAID: 10027699047
  • Peer Reviewed
• [Journal Article] Expression of MSX2 predicts malignancy of branch duct intraductal papillary mucinous neoplasm of the pancreas. (2010)
  • Author(s): Satoh K, Hamada S, Kanno A, Hirota M, Umino J, Ito H, Masamune A, Egawa S, Unno M, Shimosegawa T.
  • Journal Title: J Gastroenterol. Jan 28(Epub)
  • NAID: 10026707200
  • Peer Reviewed
• [Journal Article] Chronic pancreatitis and pancreatic cancer : prediction and mechanism. (2009)
  • Author(s): Shimosegawa T, Kume K, Satoh K.
  • Journal Title: Clin Gastroenterol Hepatol. 7(11Suppl)
  • Peer Reviewed
• [Journal Article] Bone marrow contributes to the population of pancreatic stellate cells in mice. (2009)
  • Author(s): Watanabe T, Masamune A, Kikuta K, Hirota M, Kume K, Satoh K, Shimosegawa T.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. 297(6)
  • Peer Reviewed
• [Journal Article] Expression of the calcium-binding protein S1OOP is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines (2009)
  • Author(s): Hamada S, Satoh K, Hirota M, Fujibuchi W, Kanno A, Umino J, Ito H, Satoh A, Kikuta K, Kume K, Masamune A. Shimosesawa T.
  • Journal Title: Cancer Sci 100 Pages: 103-110
  • Peer Reviewed
• [Journal Article] Fibrinogen induces cytokine and collagen production in pancreatic stellate cells (2009)
  • Author(s): Masamune A, Kikuta K, Watanabe T, Satoh K, Hirota M, Hamada S, Shimosegawa T
  • Journal Title: Gut 58 Pages: 550-559
  • Peer Reviewed
• [Journal Article] Hypoxia stimulates pancreatic stellate cells to induce fibrosis and angiogenesis in pancreatic cancer (2008)
  • Author(s): Masamune A, Kikuta K, Watanabe T, Satoh K, Hirota M, Shimosegawa T
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 295 Pages: 709-717
  • Peer Reviewed
• [Presentation] THE TRANSCRIPTIONAL REGULATION OF CANCER STEM CELL-RELATED GENE ABCG2 BY THE HOMEOBOX GENE MSX2. (2011)
  • Author(s): Hamada S, Satoh K,, Hirota M, Kanno A, Masamune A, Kikuta K, Kume K, Unno J, Shimosegawa T.
  • Organizer: International Association of Pancreatology & Indian Pancreas Club 2011
  • Place of Presentation: Cochin, India
  • Year and Date: 2011-02-13
• [Presentation] ホメオボックス遺伝子MSX2はトランスポーター遺伝子ABCG2の転写を制御することによりstelm cell-like phenotypeを規定する (2010)
  • Author(s): 濱田晋 佐藤賢一 下瀬川徹
  • Organizer: JDDW2010
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-14
• [Presentation] The regulation of stem cell related genes by the homeobox gene MSX2 in pancreatic cancer cells. (2010)
  • Author(s): Hamada S, Satoh K, Hirota M, Kanno A, Ito H, Shimosegawa T.
  • Organizer: DDW 2010
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2010-05-02
• [Presentation] ヒト膵癌におけるstem cell-like phenotypeとmicroRNA発現プロファイル (2010)
  • Author(s): 濱田晋, 佐藤賢一, 下瀬川徹
  • Organizer: 第96回 消化器病学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-23
• [Presentation] ホメオボックス遺伝子MSX2はトランスポーター遺伝子ABCG2の転写を制御することによりstem cell-like phenotypeを規定する (2009)
  • Author(s): 濱田晋, 佐藤賢一, 下瀬川徹
  • Organizer: JDDW2009
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] 膵癌細胞株におけるBMP4によるカルシウム結合蛋白S100Pの発現誘導とその機能についての検討 (2008)
  • Author(s): 濱田晋, 佐藤賢一, 廣田衛久, 菅野敦, 海野純, 伊藤広通, 下瀬川徹
  • Organizer: 第50回日本消化器病学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-03