Prospective isolation of pancreatic cancer cells with highly malignant phenotype and development of future individualized therapy

• Project/Area Number: 21390381
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: TANAKA Masao 九州大学, 医学研究院, 教授 (30163570)
• Co-Investigator(Kenkyū-buntansha): SATO Norihiro 九州大学, 大学院・医学研究院, 共同研員 (20423527) ; OHUCHIDA Kenoki 九州大学, 大学院・医学研究院, 講師 (20452708) ; TOMA Hiroki 九州大学, 大学病院, 講師 (80437780) ; 冨永 洋平 九州大学, 大学院・医学研究院, 特任講師 (90304823)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 膵臓外科学 / 膵癌 / セルソーティング / 癌間質相互作用 / 上皮間葉移行(EMT) / セルソーテング

Research Abstract

We identified CD133 positive pancreatic cancer cells with high malignant potential. CD133 positive pancreatic cancer cells have strong invasive ability via SDF1-CXCR4 pathway. We also found that migration of CD105 positive pancreatic cancer cells was promoted by cancer-stromal interactions. Moreover, we clarified that collagen-internalization receptor CD280 was an important molecule for invasion of pancreatic cancer cells. We reduced the invasion of pancreatic cancer cells by knockdown of CD280. In the present study, we identified several molecules as promising therapeutic targets.

Research Products

• [Journal Article] High EGFR mRNA Expression Level is a Prognostic Factor for Reduced Survival in Pancreatic Cancer after Gemcitabine-based Adjuvant Chemotherapy International Journal of Oncology (2011)
  • Author(s): Hayato Fujita, Kenoki Ohuchida, Kazuhiro Mizumoto, Soichi Itaba, Tetsuhide Ito, Kohei Nakata, Jun Yu, Tadashi Kayashima, Akifumi Hayashi, Ryota Souzaki, Tatsuro Tajiri, Manabu Onimaru, Tatsuya Manabe, Takao Ohtsuka, Masao Tanaka
  • Volume: 38
  • Pages: 629-41
• [Journal Article] Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia Cancer Science (2011)
  • Author(s): Tadashi Kayashima, Kohei Nakata, Kenoki Ohuchida*, Hayato Fujita, Cui Lin, Kazuhiro Mizumoto, Masao Tanaka
  • Volume: 102
  • Pages: 1137-43
• [Journal Article] Enhanced cell migration and invasion of CD133(+) pancreatic cancer cells cocultured with pancreatic stromal cells (2010)
  • Author(s): Taiki Moriyama, Kenoki Ohuchida, Kazuhiro Mizumoto, Lin Cui, Naoki Ikenaga, Norihiro Sato, Masao Tanaka
  • Journal Title: Cancer Volume: 116(14) Pages: 3357-3368
• [Journal Article] CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer (2010)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida, Kazuhiro Mizumoto, Lin Cui, Tadashi Kayashima, Katsuya Morimatsu, Taiki Moriyama, Kohei Nakata, Hayato Fujita, Masao Tanaka
  • Journal Title: Gastroenterology Volume: 139 Pages: 1041-1051
• [Journal Article] Characterization of CD24 expression in intraductal papillary mucinous neoplasms and ductal carcinoma of the pancreas (2010)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida, Kazuhiro Mizumoto, Jun Yu, Tadashi Kayashima, Akifumi Hayashi, Kohei Nakata, Masao Tanaka
  • Journal Title: Hum Pathol Volume: 41 Pages: 1466-1474
• [Journal Article] Enhanced cell migration and invasion of CD133^+ pancreatic cancer cells co-cultured with pancreatic stromal cells (2010)
  • Author(s): Taiki Moriyama, Kenoki Ohuchida, Kazuhiro Mizumoto, Lin Cui, Naoki Ikenaga, Norihiro Sato, Masao Tanaka
  • Journal Title: Cancer Volume: 116 Pages: 3357-3368
  • Peer Reviewed
• [Journal Article] Characterization of CD24 expression in intraductal papillary mucinous neoplasms and ductal carcinoma of the pancreas. (2010)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida, Kazuhiro Mizumoto, Jun Yu, Tadashi Kayashima, Akifumi Hayashi, Kohei Nakata, Masao Tanaka.
  • Journal Title: Human Pathology Volume: 41 Pages: 1466-1474
  • Peer Reviewed
• [Journal Article] Enhanced cell migration and invasion of CD133+ pancreatic cancer cells co-cultured with pancreatic stromal cells (2010)
  • Author(s): Taiki Moriyama, Kenoki Ohuchida, Kazuhiro Mizumoto, Lin Cui, Naoki Ikenaga, Norihiro Sato, Masao Tanaka
  • Journal Title: Cancer (in press)
  • Peer Reviewed
• [Presentation] The Functional Heterogeneity of Pancreatic Cancer Cells and Surrounding Stromal Cells in Cancer-Stromal Interactions (2011)
  • Author(s): Ohuchida K., et al
  • Organizer: The 4th International Conference for Treatment, of Pancreatic Cancer
  • Place of Presentation: Taipei, Taiwan(招待講演)
  • Year and Date: 2011-06-25
• [Presentation] Pancreatic Stellate Cells Promote Migration of CD105+ Pancreatic Cancer Cells (2011)
  • Author(s): Taipei, Taiwan
  • Organizer: 42^<nd> American Pancreatic Association(APA) Annual Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] 膵癌細胞は癌間質相互作用により細胞外基質コラーゲンを取り込み、浸潤を促進する (2011)
  • Author(s): 池永直樹、大内田研宙、小薗真吾、Prawej Mahawithitwong、大塚隆生、水元一博、田中雅夫
  • Organizer: 第22回日本消化器癌発生学会総会
  • Place of Presentation: 佐賀
• [Presentation] 膵癌細胞株による放射線治療抵抗性と上皮間葉移行の関連性の検討 (2011)
  • Author(s): 小薗真吾、大内田研宙、高浪英樹、江口大樹、藤原謙次、趙茖、崔林、池永直樹、坂井寛、藤田逸人、大塚隆生、水元一博、田中雅夫
  • Organizer: 第47回九州外科学会
  • Place of Presentation: 宮崎宮崎宮崎宮崎宮崎
• [Presentation] Pancreatic Stellate Cells Promote Migration of CD105+ Pancreatic Cancer Cells (2011)
  • Author(s): Fujiwara K., et,al
  • Organizer: 42^<nd> American Pancreatic Association (APA) Annual Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] 膵癌細胞株による放射線治療抵抗性と上皮間葉移行の関連性の検討 (2011)
  • Author(s): 小薗真吾, 他
  • Organizer: 第48回九州外科学会
  • Place of Presentation: 宮崎
• [Presentation] Characterization of CD24 Expression in Intraductal Papillary Mucinous Neoplasms and Ductal Carcinoma of the Pancreas (2010)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida, Hayato Fujita, Kazuhiro Mizumoto, Masao Tanaka
  • Organizer: 41^<st> Annual Meeting of the American Pancreatic Association
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2010-11-04
• [Presentation] Characterization of CD24 Expression in Intraductal Papillary Mucinous Neoplasms and Ductal Carcinoma of the Pancreas. (2010)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida, Hayato Fujita, Kazuhiro Mizumoto, Masao Tanaka.
  • Organizer: 41^<st> Annual Meeting of the American Pancreatic Association Chicago
  • Place of Presentation: Chicago, IL, USA.
  • Year and Date: 2010-11-04
• [Presentation] The Functional Heterogeneity of Pancreatic Cancer Cells and Surrounding Stromal Cells in Cancer-Stromal Interactions The 4th International Conference for Treatment of Pancreatic Cancer (2010)
  • Author(s): Kenoki Ohuchida, Kazuhiro Mizumoto, Masao Tanaka
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2010-06-05
• [Presentation] CD133+ cells are resistant to anoikis in pancreatic cancer (2009)
  • Author(s): T.Moriyama, K.Ohuchida, C.Lin, N.Ikenaga, H.Sakai, K.Mizumoto, M.Tanaka
  • Organizer: the Joint 40th Anniversary Meeting of American Pancreatic Association and Japan Pancreas Society
  • Place of Presentation: 米国(ハワイ)
• [Presentation] 膵癌におけるCD133陽性細胞は、癌間質作用を介してより高い遊走・浸潤能を獲得する. (2009)
  • Author(s): 森山大樹, 大内田研宙, 水元一博, 崔林, 余俊, 江上拓哉, 藤田逸人, 佐藤典宏, 当間宏樹, 永井英司, 田中雅夫
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Book] 膵癌における癌間質相互作用特集:膵癌診療と研究の最先端胆と膵 (2011)
  • Author(s): 大内田研宙、大塚隆生、水元一博、田中雅夫
• [Book] Molecular biology-based diagnosis and therapy for pancreatic cancer Fukuoka Igaku Zasshi (2011)
  • Author(s): Fujita H, Ohuchida K, Mizumoto K, Tanaka M
• [Book] 膵癌の分子生物学的解析の現状腫瘍内科 (2011)
  • Author(s): 大内田研宙、藤田逸人、水元一博、田中雅夫
• [Book] 特集/膵嚢胞性疾患の新展開I.嚢胞性膵腫瘍の基礎2.分子生物マーカー:biomarker 肝胆膵 (2010)
  • Author(s): 大内田研宙、水元一博、藤田逸人, 大塚隆生、田中雅夫
• [Book] 膵癌の分子生物学的解析に基づく個別化治療に向けた取り組み胆と膵 (2010)
  • Author(s): 大内田研宙、大塚隆生、水元一博、田中雅夫
• [Book] 分子発現解析に基づく膵癌診断法とその意義 特集『膵癌に対するトランスレーショナルリサーチの展望』 膵臓 (2010)
  • Author(s): 大内田研宙、大塚隆生、水元一博、田中雅夫