Generation of artificial pancreatic cancer stem cell and its regulation by microRNA in order to develop effective therapy for pancreatic cancer.

• Project/Area Number: 24591022
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: KENNICHI Satoh 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん幹細胞研究部, 部長 (10282055)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膵癌 / 人工がん幹細胞 / マイクロＲＮＡ / 人工癌幹細胞 / EMT

Outline of Final Research Achievements

In order to develop effective therapy for pancreatic cancer, we tried to generate artificial pancreatic cancer stem cell. Human pancreatic duct cell line (HPDE) transfected with expression vector of activated K-ras demonstrated the increased sphere formation but could not show the increase in number of cancer stem cell marker positive cells. PKM2, a key molecule for Warburg effect, was significantly expressed in pancreatic cancer cells compared to normal cells. In addition, suppression of PKM2 expression resulted in decreased cellular growth. During the exploration for microRNA associated with cancer stem cell property, miR-483-3p was identified as highly expressed microRNA in pancreatic cancer cells.

Research Products

• [Journal Article] CUB-domain containing protein 1 represses the epithelial phenotype of pancreatic cancer cells (2014)
  • Author(s): Miura S, Hamada S, Masamune A, Satoh K, Shimosegawa T
  • Journal Title: Exp Cell Res Volume: 321(2) Issue: 2 Pages: 209-218
  • DOI: 10.1016/j.yexcr.2013.12.019
  • Peer Reviewed
• [Journal Article] Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. (2014)
  • Author(s): Abue, M., Yokoyama, M., Shibuya, R., Tamai, K., Yamaguchi, K., Sato, I., Tanaka, N., Hamada, S., Shimosegawa, T., Sugamura, K., Satoh, K.
  • Journal Title: Int J Oncol Volume: 10 Issue: 2 Pages: 1-9
  • DOI: 10.3892/ijo.2014.2743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX (2014)
  • Author(s): Hamada S, Masamune A, Miura S, Satoh K, Shimosegawa T
  • Journal Title: Cell Signal Volume: 26(2) Issue: 2 Pages: 179-185
  • DOI: 10.1016/j.cellsig.2013.11.003
  • Peer Reviewed
• [Journal Article] Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. (2013)
  • Author(s): Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K.
  • Journal Title: PlosONE Volume: 8 Issue: 10 Pages: e77070-e77070
  • DOI: 10.1371/journal.pone.0077070
  • Peer Reviewed
• [Journal Article] miR-197 induces epithelialmesenchymal transition in pancreatic cancer cells by targeting p120 catenin. J Cell Physiol (2013)
  • Author(s): Hamada S, et al
  • Journal Title: J Cell Physiol Volume: 228(6) Issue: 6 Pages: 1255-63
  • DOI: 10.1002/jcp.24280
  • Peer Reviewed
• [Presentation] The Evaluation of Circulating miR-483-3p and miR-21 in Plasma of Pancreatic Ductal Adenocarcinoma Patients. (2014)
  • Author(s): 3)M, Abue, M. Yokoyama, R. Shibuya, K.Tamai, I. Sato, N. Tanaka, K. Yamaguchi, S. Hamada, T. Shimosegawa, K. Sugamura, K. Satoh.
  • Organizer: 45th Anniversarry meeting of American pancreatic association/Japanese pancreatic society.
  • Place of Presentation: Big Island, Hawai.
  • Year and Date: 2014-11-05 – 2014-11-08
• [Presentation] Pyruvate Kinase Type M2 (PKM2) Is Selectively Expressed and Involved in Survival and Development in Pancreatic Ductal Adenocarcinoma Cells. (2014)
  • Author(s): M. Yokoyama，R. Shibuya，T. Shiroki，N. Tanuma，K. Tamai，K. Yamaguchi，N. Tanaka，K. Sugamura，K. Satoh
  • Organizer: 45th Anniversarry meeting of American pancreatic association/Japanese pancreatic society.
  • Place of Presentation: Big Island, Hawai.
  • Year and Date: 2014-11-05 – 2014-11-08
• [Presentation] ピルビン酸キナーゼM2(PKM2)は膵癌で高発現し、細胞増殖能を亢進させる (2014)
  • Author(s): 2)横山 美沙、白木 健悠、田沼 延公、玉井 恵一、山口 壹範、田中 伸幸、菅村 和夫、佐藤 賢一
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 血漿中マイクロRNA発現解析の膵癌診断に対する有用性の検討 (2014)
  • Author(s): 1)虻江誠、鈴木雅貴、塚本啓裕、濱田晋、下瀬川徹、佐藤賢一
  • Organizer: 第45回日本膵臓学会大会
  • Place of Presentation: 小倉
  • Year and Date: 2014-07-11 – 2014-07-12
• [Presentation] トピックセッション 膵癌の克服を目指した基礎研究 (2013)
  • Author(s): 佐藤賢一、濱田晋、下瀬川徹
  • Organizer: 第４４回 日本膵臓学会大会
  • Place of Presentation: 仙台市
  • Invited
• [Presentation] 浸潤性膵癌特異的oncomiRであるmiR197はVDAC1発現を制御し後期的解糖を促進する (2013)
  • Author(s): 濱田晋、佐藤賢一、正宗淳、菅野敦、菊田和宏、粂潔、廣田衛久、下瀬川徹
  • Organizer: 第４４回 日本膵臓学会大会
  • Place of Presentation: 仙台市
• [Presentation] 膵癌における血漿中miR-483-3p の発現解析 (2013)
  • Author(s): 虻江誠、濱田晋、玉井恵一、田中伸幸、山口壹範、菅村和夫、佐藤郁郎、
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜市
• [Presentation] Identification of invasion-related microRNAs in pancreatic cancer by comprehensive analysis. (2012)
  • Author(s): Hamada S, Satoh K, Hirota M, Kanno A, Masamune A, Kikuta K, Kume K, Unno J, Shimosegawa T.
  • Organizer: 20Th United European Gastroenterology Week
  • Place of Presentation: Amsterdam, Netherland