Epigeneticregulation of genes related to pancreatic cancer stem cells and its clinical application

• Project/Area Number: 22591522
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Occupational and Environmental Health, Japan (2012); Kyushu University (2010-2011)
• Principal Investigator: SATO Norihiro 産業医科大学, 医学部, 助教 (20423527)
• Co-Investigator(Kenkyū-buntansha): TANAKA Masao 九州大学, 医学研究院, 教授 (30163570) ; TOMINAGA Yohei 九州大学, 医学研究院, 特任講師 (90304823) ; TAKAHATA Shunichi 九州大学, 大学病院, 助教 (50437779) ; TSUTSUMI Kosuke 九州大学, 大学病院, 医員 (00467937)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 膵癌 / 癌幹細胞 / 幹細胞 / メチレーション

Research Abstract

The aim of thisstudy was to investigate the epigenetic regulation of genes related to the phenotype of pancreatic cancer stem cells. First, we planned to purify pancreaticcancer stem cellpopulation by sorting cellsusing specific cellsurface markers. Then, we used a genome-wide apProach to identify DNA nlethylation nlarkers in the subpopulation of pancreatic cancer stem cells. We already have a list of genes that may be regulated primarily by DNA methylation in pancreatic cancer stem cell population. Finally, we are planning to validate these DNA methylation markers identified through the genome-wide approach and to further investigate the functional relevance of each DNA marker.

Research Products

• [Journal Article] MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXAl gene (2012)
  • Author(s): Ohuchida K, Mizumoto K, Lin C,Yanlaguchi H, Ohtsuka T, Sato N, Toma H, Nakamura M, Nagai E, Hashizume M et al
  • Journal Title: Ann Surg Oncol Volume: 19(7) Pages: 2394-2402
  • Peer Reviewed
• [Journal Article] Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma (2012)
  • Author(s): Tsutsumi K, Sato N, Tanabe R, Mizumoto K, Morimatsu K, Kayashima T,Fujita H, Ohuchida K, Ohtsuka T, Takahata S et al
  • Journal Title: Ann Surg Oncol Volume: 19 Suppl 3
  • Peer Reviewed
• [Journal Article] MicroRNA-10a is Overexpressed in Human Pancreatic Cancer and Involved in Its Invasiveness Partially via Suppression of the HOXA1 Gene (2012)
  • Author(s): Ohuchida K, Mizumoto K, Lin C, Yamaguchi H, Ohtsuka T, Sato N, Toma H, Nakamura M, Nagai E, Hashizume M, Tanaka M.
  • Journal Title: Ann Surg Oncol Volume: 19(7) Issue: 7 Pages: 2394-2402
  • DOI: 10.1245/s10434-012-2252-3
  • Peer Reviewed
• [Journal Article] Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas (2011)
  • Author(s): Tsutsumi K, Sato N, Cui L, Mizumoto K, Sadakari Y, Fujita H, Ohuchida K,Ohtsuka T, Takahata S, Tanaka M
  • Journal Title: Mod Pathol 2011 Volume: 24(4) Pages: 533-541
  • Peer Reviewed
• [Journal Article] Claudin-4 Expression Predicts Survival in Pancreatic Ductal Adenocarcinoma (2011)
  • Author(s): Tsutsumi K, et al
  • Journal Title: Ann Surg Oncol Volume: (in press)(未定) Issue: S3 Pages: 491-499
  • DOI: 10.1245/s10434-011-1970-2
  • Peer Reviewed
• [Journal Article] Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells (2010)
  • Author(s): Cui L, Ohuchida K, Mizumoto K, Moriyama T, Onimaru M, Nakata K, Nabae T, Ueki T, Sato N, Tominaga Y et al
  • Journal Title: PLoS One Volume: 5(8)
  • Peer Reviewed
• [Journal Article] SPARC mRNA expression as a prognostic marker for pancreatic adenocarc inoma patients (2010)
  • Author(s): Miyoshi K, Sato N, Ohuchida K, Mizumoto K, Tanaka M
  • Journal Title: Anticancer Res Volume: 30(3) Pages: 867-871
  • Peer Reviewed
• [Journal Article] Enhanced cell migration and invasion of CD133+ pancreatic cancer cells cocultured with pancreatic stromal cells (2010)
  • Author(s): Moriyama T, Ohuchida K, Mizumoto K, Cui L, Ikenaga N, Sato N, Tanaka M
  • Journal Title: Cancer 2010 Volume: 116(14) Pages: 3357-3368
  • Peer Reviewed
• [Journal Article] Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer (2010)
  • Author(s): Onimaru M, Ohuchida K, Nagai E, Mizumoto K, Egami T, Cui L, Sato N, Uchino J, Takayama K, Hashizume M et al
  • Journal Title: Cancer Lett 2010 Volume: 294(2) Pages: 178-186
  • Peer Reviewed
• [Journal Article] MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation (2010)
  • Author(s): Yu J, Ohuchida K, Mizumoto K, Sato N,Kayashima T, Fujita H, Nakata K, Tanaka M
  • Journal Title: Mol Cancer 2010 Volume: 9 Pages: 169-169
  • Peer Reviewed
• [Journal Article] 膵癌の増殖・進展に関わるシグナル経路研究と臨床展開】 Other signals related to pancreatic cancer膵癌の増殖・進展におけるRELN pathwayの関与 (2010)
  • Author(s): 佐藤典宏
  • Journal Title: 塀・担・搾2010 Volume: 61(1) Pages: 81-90
  • Peer Reviewed
• [Journal Article] Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells (2010)
  • Author(s): Cui L, Ohuchida K, MizumotoK, Moriyama T, Onimaru M, Nakata K, Nabae T, Ueki T, Sato N, Tominaga Y, Tanaka M.
  • Journal Title: PLoS One Volume: 12 Pages: 1-11
  • Peer Reviewed
• [Journal Article] Enhanced cell migration and invasion of CD133+ pancreatic cancer cells cocultured with pancreatic stromal cells. (2010)
  • Author(s): Moriyama T, Ohuchida K, Mizumoto K, Cui L, Ikenaga N, Sato N, Tanaka M.
  • Journal Title: Cancer Volume: 15 Pages: 3357-68
  • Peer Reviewed
• [Presentation] claudin-4発現は膵癌の予後予測因子として有用である (2011)
  • Author(s): 堤宏介,佐藤典宏,大内田研宙,大塚隆生,高畑俊一,中村雅史,水元一博,田中雅夫
  • Organizer: 第49回日本癌治療学会学術総会 (シンポジウム)
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-28
• [Presentation] 膵液中でのclaudin-4(CLDN4)発現解析は腸型IPMNの術前診断に有用である (2011)
  • Author(s): 堤宏介,佐藤典宏,森泰寿,安井隆晴,大内田研宙,大塚隆生,高畑俊一,中村雅史,水元一博,田中雅夫
  • Organizer: 第111回日本外科学会定期学術集, (紙上開催)
  • Place of Presentation: 東京都