Targeting therapy using chemotherapy-resistant pancreatic cancer stem cells

• Project/Area Number: 23592007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kobe University
• Principal Investigator: SHIMIZU Kazuya 神戸大学, 保健学研究科, 研究員 (50335353)
• Co-Investigator(Kenkyū-buntansha): HORI Yuichi 神戸大学, 保健学研究科, 教授 (80248004)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 膵臓がん / がん幹細胞 / 癌幹細胞 / 膵臓癌 / 微小環境

Research Abstract

Pancreatic ductal adenocarcinoma is highly resistant to systemic chemotherapy. tabine-resistant pancreatic ductal adenocarcinoma patients. By use of in vitro co-culture system with stromal cells, we established a novel pancreatic tumor-initiating cell line. The cell line required its direct interaction with stromal cells for its in vitro clonogenic growth and passaging. Their direct interaction induced basal lamina-like extracellular matrix formation that maintained colony formation. The cell line expressed CD133 protein, which expression level changed autonomously and by culture conditions. These results demonstrated that there were novel pancreatic tumor-initiating cells that required direct interactions with stromal cells for their in vitro cultivation in gemcitabine-resistant pancreatic ductal adenocarcinoma. This cell line would help to develop novel therapies that enhance effects of gemcitabine or novel anti-cancer drugs.

Research Products

• [Journal Article] Establishment of a novel cell line from intraductal papillary neoplasm of the bile duct. (2014)
  • Author(s): Murakami S, Ajiki T, Hori Y, Okazaki T, Fukumoto T, Ku Y.
  • Journal Title: Anticancer Research Volume: 34 Pages: 2203-2209
  • NAID: 120005970749
  • Peer Reviewed
• [Journal Article] Identification of a novel subpopulation of tumor-initiating cells from gemcitabine-resistant pancreatic ductal adenocarcinoma patients. (2013)
  • Author(s): Shimizu K, Chiba S, Hori Y.
  • Journal Title: PLoS One. Volume: 21 Issue: 11 Pages: e81283-e81283
  • DOI: 10.1371/journal.pone.0081283
  • NAID: 120005356910
  • Peer Reviewed
• [Journal Article] Prominin-1 (CD133) Reveals New Faces of Pancreatic Progenitor Cells and Cancer Stem Cells: Current Knowledge and Therapeutic Perspectives. (2013)
  • Author(s): Hori Y.
  • Journal Title: Adv Exp Med Biol. Volume: 777 Pages: 185-196
  • DOI: 10.1007/978-1-4614-5894-4_12
  • ISBN: 9781461458937, 9781461458944
  • Peer Reviewed
• [Journal Article] Distinct expression of CD133 between intraductal papillary neoplasms of the bile duct and bile duct adenocarcinomas (2012)
  • Author(s): Ohtsubo I, Ajiki T, Hori Y, Murakami S, Shimizu K, Fukumoto T, Ku Y.
  • Journal Title: Hepatol Res. Volume: Vol.42 Pages: 574-582
  • NAID: 10031144272
  • Peer Reviewed
• [Journal Article] Distinctive expression of CD133 between intraductal papillary neoplasms of the bile duct and bile duct adenocarcinomas. (2012)
  • Author(s): ohtsubo I
  • Journal Title: Hepatology Research Volume: 42 Issue: 6 Pages: 574-582
  • DOI: 10.1111/j.1872-034x.2011.00954.x
  • Peer Reviewed
• [Presentation] Gemcitabineが初代膵癌細胞に及ぼす効果の検討 (2013)
  • Author(s): 藤原範人、堀裕一
  • Organizer: 第45回日本臨床分子形態学会
  • Place of Presentation: 福岡
  • Year and Date: 2013-09-13
• [Presentation] 膵組織幹細胞を用いた再生医療研究 (2013)
  • Author(s): 堀裕一、清水一也
  • Organizer: 第44回日本膵臓学会
  • Place of Presentation: 山形
  • Year and Date: 2013-07-25
• [Presentation] 膵組織幹細胞を用いた再生医療研究 (2013)
  • Author(s): 堀裕一
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台
• [Presentation] 糖尿病の再生医療を目指したインスリン産生細胞の誘導 (2013)
  • Author(s): 神農祐樹、片山南詩、山崎千寛、平井里奈、藤原範人、三浦拓真、上野山恭平、西山嵩晃、堀裕一
  • Organizer: 第8回日本臨床検査学教育学会
  • Place of Presentation: 大阪
• [Presentation] Gemcitabineが初代膵癌細胞に及ぼす効果の検討 -新規治療薬の開発をめざして- (2013)
  • Author(s): 藤原範人、清水一也、西山嵩晃、片山南詩、神農祐樹、平井里奈、三浦拓真、上野山恭平、山崎千寛、堀裕一
  • Organizer: 第45回日本臨床分子形態学会
  • Place of Presentation: 福岡
• [Presentation] 幹細胞マーカーラベルマウスを用いた膵再生医療研究 (2013)
  • Author(s): 堀裕一
  • Organizer: JDDW
  • Place of Presentation: 東京
• [Presentation] 膵癌の進展機構における組織幹細胞の関与 (2012)
  • Author(s): 堀裕一、清水一也
  • Organizer: 第43回日本膵臓学会
  • Place of Presentation: 山形
  • Year and Date: 2012-06-28
• [Presentation] Direct interaction between human pancreatic cancer stem cells and stromal cells remodels extracellular matrix formation for cancer stem cell niche (2012)
  • Author(s): Shimizu K.
  • Organizer: 10^<th> International Society for Stem Cell Research
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-13
• [Presentation] Direct interaction between pancreatic cancer stem cells and stromal cells remodels extracellular matrix formation for cancer stem cell niche (2012)
  • Author(s): Hori Y, Shimizu K.
  • Organizer: 103^<rd> American Association for Cancer Research
  • Place of Presentation: Chicago, USA
  • Year and Date: 2012-04-01
• [Presentation] Direct interaction between human pancreatic cancer stem cells and stromal cells remodels extracellular matrix formation for cancer stem cell niche. (2012)
  • Author(s): Shimizu K
  • Organizer: 10th International Society for Stem Cell Research
  • Place of Presentation: Yokohama
• [Presentation] Direct interaction between human pancreatic cancer stem cells and stromal cells remodels extracellular matrix formation for cancer stem cell niche. (2012)
  • Author(s): Hori Y
  • Organizer: 103rd American Association for Cancer Research
  • Place of Presentation: Chicago, USA
• [Presentation] Direct interaction between human pancreatic cancer stem cells and stromal cells remodels extracellular matrix formation for cancer stem cell niche. (2012)
  • Author(s): 堀裕一、清水一也、中村幸恵
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Chicago
• [Book] 肝胆膵 (2013)
  • Author(s): 堀裕一
  • Total Pages: 734
  • Publisher: アークメディア
• [Book] 肝胆膵 (2013)
  • Author(s): 堀裕一
  • Publisher: アークメディアクメディア