The development of therapy of pancreatic cancer stem cells and the surrounding stromal cells.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20689026
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: OHUCHIDA Kenoki 九州大学, 医学研究院, 客員助教 (20452708)
• Project Period (FY): 2008 – 2010
• Keywords: 癌幹細胞 / 膵癌 / ニッチ / 癌間質相互作用 / 治療抵抗性

Research Abstract

In the present study, we investigated the pancreatic cancer stem cells and the surrounding stromal cells and found that a specific cell population of stromal cells, CD10 positive pancreatic stellate cells, have an important role in the cancer-stromal interaction during pancreatic cancer progression. We also investigated the mechanisms of the promoting effects of CD10 positive cells on the enhancement of invasion of pancreatic cancer cells, and found that MMP3 is implicated in this mechanism. These data suggest that there is heterogeneity among pancreatic stellate cells and a specific subpopulation of these cells has more important role in cancer progression.

Research Products

• [Journal Article] Manabu Onimaru, Tatsuya Manabe, Takao Ohtsuka (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
  • Journal Title: Masao Tanaka High EGFR mRNA Expression Level is a Prognostic Factor for Reduced Survival in Pancreatic Cancer after Gemcitabine-based Adjuvant Chemotherapy International Journal of Oncology Volume: 38 Pages: 629-41
• [Journal Article] Masao Tanakaα-SMA expressing stroma promotes an aggressive tumor-biology in pancreatic ductal adenocarcinoma (2010)
  • Author(s): Hayato Fujita, Kenoki Ohuchida*, Kazuhiro Mizumoto, Kohei Nakata, Jun Yu, Tadashi Kayashima, Manabe Tatsuya, Ohtsuka Takao
  • Journal Title: Pancreas Volume: 39 Pages: 1254-62
• [Journal Article] MicroRNA-203 expression is a new prognostic marker of pancreatic cancer (2010)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida*, Kazuhiro Mizumoto, Jun Yu, Tadashi Kayashima, Hayato Fujita, Kohei Nakata and Masao Tanaka
  • Journal Title: MicroRNA-203 expression is a new prognostic marker of pancreatic cancer Volume: 17 Pages: 3120-8
• [Journal Article] Expression Analyses in Preoperative Pancreatic Juice Samples of Pancreatic Ductal Adenocarcinoma (2010)
  • Author(s): Sadakari Y, Ohtsuka T, Ohuchida K, Tsutsumi K, Takahata S, Nakamura M, Mizumoto K, Tanaka M. MicroRNA
  • Journal Title: JOP Volume: 11 Pages: 587-92
• [Journal Article] Masao Tanaka MicroRNA miR-17-5p is overexpressed in pancreatic cancer, and its upregulation enhances cancer cell proliferation and invasion in vitro (2010)
  • Author(s): Jun Yu, Kenoki Ohuchida*, Kazuhiro Mizumoto, Hayato Fujita, Kouhei Nakata and Masao Tanaka
  • Journal Title: Cancer Biology & Therapy Volume: 10 Pages: 748-57
• [Journal Article] Takao Ohtsuka, Masao Tanaka Gene Expression levels as Predictive Markers of Outcome in Pancreatic Cancer after Gemcitabine-based adjuvant Chemotherapy (2010)
  • Author(s): Hayato Fujita, Kenoki Ohuchida*, Kazuhiro Mizumoto, Soichi Itaba, Tetsuhide Ito, Kohei Nakata, Jun Yu, Tadashi Kayashima, Ryota Souzaki, Tatsuro Tajiri, Tatsuya Manabe
  • Journal Title: Neoplasia Volume: 12 Pages: 801-17
• [Journal Article] Masao Tanaka Prospectively isolated (2010)
  • Author(s): Lin Cui, Kenoki Ohuchida*, Kazuhiro Mizumoto, Taiki Moriyama, Manabu Onimaru, Kohei Nakata, Toshinaga Nabae, Takashi Ueki, Norihiro Sato, Yohei Tominaga
  • Journal Title: PLos One Volume: 12 Pages: 12121
• [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, and Masao Tanaka
  • Journal Title: Gastroenterology Volume: 139 Pages: 1041-51
• [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): Jun Yu, Kenoki Ohuchida*, Kazuhiro Mizumoto*, Norihiro Sato, Tadashi Kayashima, Hayato Fujita, Kouhei Nakata, and Masao Tanaka
  • Journal Title: Molecular Cancer Volume: 28 Pages: 9-169
• [Journal Article] Characterization of CD24 expression in intraductal papillary mucinous neoplasms and pancreatic cancer (2010)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida*, Kazuhiro Mizumoto, Jun Yu, Tadashi Kayashima, Akifumi Hayashi, Kohei Nakata, and Masao Tanaka
  • Journal Title: Human Pathology Volume: 41 Pages: 1466-74
• [Journal Article] S100P is a novel marker to identify invasive lesion in intraductal papillary mucinous neoplasms (2010)
  • Author(s): Kohei Nakata, Eishi Nagai, Kenoki Ohuchida, Shinichi Aishima, Akifumi Hayashi, Yoshihiro Miyasaka, Jun Yu, Kazuhiro Mizumoto, Masao Tanaka, and Masazumi Tsuneyoshi
  • Journal Title: Human Pathology Volume: 41 Pages: 824-31
• [Journal Article] Effectiveness of basic endoscopic surgical skill training for pediatric surgeons (2010)
  • Author(s): Ieiri S, Nakatsuji T, Higashi M, Akiyoshi J, Uemura M, Konishi K, Onimaru M, Ohuchida Kenoki, Hong J, Tomikawa M, Tanoue K, Hashizume M, Taguchi T
  • Journal Title: Pediatr Surg Int Volume: 26 Pages: 947-54
• [Journal Article] Invasive carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derivedfrom the intestinal type (2010)
  • Author(s): Yoshihiko Sadakari, Kenoki Ohuchida, Kohei Nakata, Tadashi Kayashima, Shinichi Aishima, Shunichi Takahata, Masafumi Nakamura, Kazuhiro Mizumoto, and Masao Tanaka
  • Journal Title: Surgery Volume: 147 Pages: 812-7
• [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, and Masao Tanaka
  • Journal Title: Cancer Volume: 116 Pages: 3357-68
• [Journal Article] synergistically enhances the effects of adenovirus gene therapy via activation of the CMV promoter in pancreatic cancer cells (2010)
  • Author(s): Manabu Onimaru, Kenoki Ohuchida*, Takuya Egami, Kazuhiro Mizumoto, Eishi Nagai, Lin Cui, Hiroki Toma, Kunio Matsumoto, Makoto Hashizume, and Masao Tanaka Gemcitabine
  • Journal Title: Cancer Gene Therapy Volume: 17 Pages: 541-9
• [Journal Article] Gemcitabine synergistically enhances cytotoxicity of hTERT promoter-dependent conditionally replicative adenovirus in pancreatic cancer cells (2010)
  • Author(s): Manabu Onimaru, Kenoki Ohuchida*, Eishi Nagai, Kazuhiro Mizumoto, Takuya Egami, Lin Cui, Norihiro Sato, Junji Uchino, Koichi Takayama, Makoto Hashizume, Masao Tanaka
  • Journal Title: Cancer Letter Volume: 294 Pages: 178-86
• [Journal Article] hTERT-promoter dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells (2010)
  • Author(s): Onimaru Manabu, Ohuchida Kenoki*, Mizumoto Kazuhiro, Nagai Eishi, Cui Lin, Toma Hiroki, Takayama Koichi, Matsumoto Kunio, Hashizume Makoto, Tanaka Masao
  • Journal Title: Cancer Science Volume: 101 Pages: 735-42
• [Journal Article] SPARC mRNA Expression as a prognostic Marker for pancreatic adenocarcinoma patients (2010)
  • Author(s): Kei Miyoshi, Norihiro Sato, Kenoki Ohuchida, Kazuhiro Mizumoto and MasaoTanaka
  • Journal Title: Anticancer Research Volume: 30 Pages: 867-71
• [Journal Article] assessment using a virtual reality simulator, LapSim, after training to develop fundamental skills for endoscopic surgery (2010)
  • Author(s): Tanoue K, Uemura M, Kenmotsu H, Ieiri S, Konishi K, Ohuchida Kenoki, Onimaru M, Nagao Y, Kumashiro R, Tomikawa M, Hashizume M. Skills
  • Journal Title: Minim Invasive Ther Allied Technol Volume: 9 Pages: 24-9
• [Journal Article] Masao Tanaka CD44v6 Expression in Intraductal Papillary Mucinous (2010)
  • Author(s): Yoshihiro Miyasaka, Eishi Nagai, Kenoki Ohuchida, Kohei Nakata, Akifumi Hayashi, Kazuhiro Mizumoto, Masazumi Tsuneyoshi
  • Journal Title: Neoplasms of the Pancreas Pancreas Volume: 39 Pages: 31-5
• [Journal Article] Tumor-stromal interactions with direct cell contacts enhance proliferation of human pancreatic carcinoma cells ; Evaluation with direct and indirect co-culture system (2009)
  • Author(s): Hayato Fujita, Kenoki Ohuchida*, Kazuhiro Mizumoto, Takuya Egami, Kei Miyoshi, Taiki Moriyama, Cui Lin, Jun Yu, Tatsuya Manabe, Masao Tanaka
  • Journal Title: Cancer Science Volume: 100 Pages: 2309-17
• [Journal Article] Intraabdominal Roux-en-Y reconstruction with a novel stapling technique after laparoscopic distal gastrectomy (2009)
  • Author(s): Noshiro H, Kenoki Ohuchida, Kawamoto M, Ishikawa M, Uchiyama A, Shimizu S, Tanaka M
  • Journal Title: Gastric Cancer Volume: 12 Pages: 164-9
• [Journal Article] MicroRNA-21(miR-21) modulates biologic functions of pancreatic cancer cells including their proliferation, invasion and chemoresistance (2009)
  • Author(s): Taiki Moriyama, Kenoki Ohuchida*, Kazuhiro Mizumoto, Jun Yu, Toshinaga Nabae, Shunichi Takahata, Norihiro Sato, Hiroki Toma, Eishi Nagai, and Masao Tanaka
  • Journal Title: Molecular Cancer Therapeutics Volume: 8 Pages: 1067-74
• [Journal Article] S100A4 mRNA is a diagnostic and prognostic marker in pancreatic carcinoma Journal of (2009)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida*, Kazuhiro Mizumoto, Jun Yu, Takuya Egami, Toshinaga Nabae, Junji Ueda, Norihiro Sato, Eishi Nagai, and Masao Tanaka
  • Journal Title: Gastrointestinal Surgery Volume: 13 Pages: 1852-8
• [Journal Article] Upregulation of integrin s3 in Radio-Resistant Pancreatic Cancer impair Adenovirus Gene Therapy (2009)
  • Author(s): Takuya Egami, Kenoki Ohuchida*, Takaharu Yasui, Kazuhiro Mizumoto, Manabu Onimaru, Hiroki Toma, Norihiro Sato, Kunio Matsumoto, and Masao Tanaka
  • Journal Title: Cancer Science Volume: 100 Pages: 1902-7
• [Presentation] 2011 at National Cheng Kung University (2011)
  • Author(s): The 4th International Conference for Treatment of Pancreatic Cancer Jun 25(Sat.)
  • Organizer: Taiwan Title
  • Place of Presentation: The functional heterogeneity of pancreatic cancer cells and surrounding stromal cells in tumor-stromal interaction
  • Year and Date: 2011-06-25
• [Presentation] Symposium 1 Kenoki Ohuchida Title (2009)
  • Author(s): The International Pancreatic Research forum 2009 Session
  • Organizer: Clinical value of mRNA expression analysis in pancreatic juice Date & Time
  • Place of Presentation: Venue : Hotel Pacific Tokyo
  • Year and Date: 2009-03-28
• [Presentation] MicroRNA-10a is Overexpressed in Human Pancreatic Cancer and Involved in its Invasiveness possibly via Suppression of the HOXA1 gene Abstract No (2008)
  • Author(s): Kenoki Ohuchida, Kazuhiro Mizumoto, Taiki Moriyama, Shunichi Takahata, Hiroki Toma, Norihiro Sato, Eishi Nagai, and Masao Tanaka
  • Organizer: 08062 the 39th Annual Meeting of the American Pancreatic Association
  • Place of Presentation: Chicago
  • Year and Date: 20081106-08
• [Presentation] CD133 positive cells in pancreatic cancer possess increased cell proliferation (2008)
  • Author(s): Taiki Moriyama, Kenoki Ohuchida, Kazuhiro Mizumoto, Cui Lin, Norihiro Sato, and Masao Tanaka
  • Organizer: migration and invasion the 39th Annual Meeting of the American Pancreatic Association
  • Place of Presentation: Chicago
  • Year and Date: 20081106-08
• [Presentation] The enhanced effect of gemcitabine on the adenovirus-mediated gene therapy the 39th Annual (2008)
  • Author(s): M. Onimaru, K. Ohuchida, E. Nagai, K. Mizumoto, T. Egami, N. Sato, H. Toma, and M. Tanaka
  • Organizer: Meeting of the American Pancreatic Association
  • Place of Presentation: Chicago
  • Year and Date: 20081106-08
• [Presentation] Associated Fibrobalasts the 39th Annual (2008)
  • Author(s): K Miyoshi, Sato N, Ohuchida K, Mizumoto K, Tanaka M Epigenetic Changes in Pancreatic Cancer
  • Organizer: Meeting of the American Pancreatic Association
  • Place of Presentation: Chicago
  • Year and Date: 20081106-08
• [Presentation] TanakaGemcitabine synergistically enhances cytotoxicity of hTERT (2008)
  • Author(s): Manabu Onimaru, Eishi Nagai, Kenoki Ohuchida, Takuya Egami, Hayato Fujita, Taiki Moriyama, Kei Miyoshi, Jun Yu, Lin Cui, Shoko Nishio, Hiroki Toma, Norihiro Sato, Kazuhiro Mizumoto, Junji Uchino, Koichi Takayama, and Masao Tanaka
  • Organizer: promoter-dependent conditionally replicative adenovirus in pancreatic cancer cells
  • Place of Presentation: Pancreatology
  • Year and Date: 20080000
• [Presentation] Quantitative analysis of hTERT mRNA levels in cells (2008)
  • Author(s): Hayato Fujita, Kenoki Ohuchida, Kazuhiro Mizumoto, Takuya Egami, Yoshihiro Miyasaka, Hiroshi Yamaguchi, Masayuki Ohta, Jun Yu, Lin Cui, Shunichi Takahata, Masazumi Tsuneyoshi, Masao Tanaka
  • Organizer: microdissected from cytological specimens
  • Place of Presentation: International Association of Pancreatology
  • Year and Date: 20080000
• [Presentation] RegIV expression is involved in'Intestinal type (2008)
  • Author(s): Kohei Nakata, Eishi Nagai, Kenoki Ohuchida, Yoshihiro Miyasaka, Akifumi Hayashi, Kazuhiro Mizumoto, Masao Tanaka and Yoshizumi Tsuneyoshi
  • Organizer: carcinogenesis of Intraductal papillary mucinous neoplasm of pancreas
  • Place of Presentation: DDW
  • Year and Date: 20080000
• [Presentation] Micro RNA(miR-17-5p) is overexpressed in pancreatic cancer (2008)
  • Author(s): Jun Yu, Taiki Moriyama, Kenoki Ohuchida, Lin Cui, Norihiro Sato, Hiroki Toma, Shunichi Takahata, Eishi Nagai, Kazuhiro Mizumoto, and Masao Tanaka
  • Organizer: and upregulation of miR-17-5p enhanced cancer cell proliferation and invasion in vitro
  • Place of Presentation: DDW
  • Year and Date: 20080000
• [Presentation] Masazumi Tsuneyoshi Senescence in intraductal papillary mucinous neoplasms of the pancreas (2008)
  • Author(s): Yoshihiro Miyasaka ; Eishi Nagai ; Kenoki Ohuchida ; Kohei Nakata ; Akifumi Hayashi ; K Mizumoto ; Masao Tanaka
  • Place of Presentation: DDW
  • Year and Date: 20080000
• [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
  • Total Pages: 131-6
• [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] 2.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」 (2010)
  • Author(s): 大内田研宙, 大塚隆生, 水元一博, 田中雅夫