Identification of the specific stromal cells in microenvironment for pancreatic cancer invasion and metastases and the development of its regulation

• Project/Area Number: 23390327
• 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: OHUCHIDA KENOKI 九州大学, 先端医療イノベーションセンター, 講師 (20452708)
• Co-Investigator(Kenkyū-buntansha): OHTSUKA Takao 九州大学, 大学病院, 助教 (20372766) ; MURATA Masaharu 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (30304744) ; SATO Norihiro 産業医科大学, 医学(系)研究科(研究院), 助教 (20423527)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 膵がん / 癌間質相互作用 / ニッチ / 膵癌 / PSC / 膵星細胞 / DDS

Research Abstract

Pancreatic cancer is one of the most deadly malignancies. Especially, the prognosis of the patients with pancreatic cancer is extremely poor. Recently, we identified the specific stromal cells responsible for invasion and/or metastasis of pancreatic cancer. In the present study, based on our previous data, we used the several stromal and endothelial markers and performed the prospective isolation of cell population derived from the resected pancreatic cancer tissues. Furthermore, we performed the functional analyses for the functional phenotyping and identified the several specific cell populations, which are significantly involved in cell proliferation, invasion, migration, EMT and metastasis of pancreatic cancer cells. We also identified the small molecules to regulate the cancer stroma and found the effect of one of the molecules in the treatment of pancreatic cancer.

Research Products

• [Journal Article] Expression of Glucagon-Like Peptide 1 Receptor and Its Effects on Biological Behavior in Pancreatic Neuroendocrine Tumors (2014)
  • Author(s): Ana Ines Cases, Takao Ohtsuka, Minoru Fujino, Noboru Ideno, Shingo Kozono, Ming Zhao, Kenoki Ohuchida, Shinichi Aishima, Masatoshi Nomura, Yoshinao Oda, Kazuhiro Mizumoto, Masao Tanaka
  • Journal Title: Pancreas Volume: 43(1) Pages: 1-6
  • Peer Reviewed
• [Journal Article] Tissue Tablet Method : An Efficient Tissue Banking Procedure Applicable to Both Molecular Analysis and Frozen Tissue Microarray (2014)
  • Author(s): Nobuhiro Torata, Kenoki Ohuchida, Shin Akagawa, Lin Cui, Shingo Kozono, Kazuhiro Mizumoto, Shinichi Aishima, Yoshinao Oda, Masao Tanaka
  • Journal Title: Human Pathology Volume: 45(1) Pages: 143-52
  • Peer Reviewed
• [Journal Article] 特集タイトル : 臨床検体から導き出す消化器病研究テーマ:6)膵液中バイオマーカーで膵疾患の診断, 早期発見はできるか (2014)
  • Author(s): 大内田研宙, 大塚隆生, 水元一博, 田中雅夫
  • Journal Title: 分子消化器病 Volume: vol.11 no.1
  • Peer Reviewed
• [Journal Article] Pancreatic Cancer: Clinical Significance of Biomarkers (2014)
  • Author(s): Mori M, Chiba T, Nakamizo A, Kumashiro R, Murata M, Akahoshi T, Tomikawa M, Ohuchida K, Ohtsuka T,Mizumoto K, Hashizume M,Tanaka M
  • Journal Title: Gastro Intestinal Tumors Volume: 1 Issue: 1 Pages: 33-40
  • DOI: 10.1159/000354996
  • Peer Reviewed
• [Journal Article] Kindlin-1 expression is involved in migration and invasion in pancreatic cancer (2013)
  • Author(s): Prawej Mahawithitwong, Kenoki Ohuchida, Naoki Ikenaga, Hayato Fujita, Ming Zhao, Shingo Kozono, Koji Shindo, Takao Ohtsuka, Shinichi Aishima, Kazuhiro Mizumoto and Masao Tanaka
  • Journal Title: International Journal of Oncology Volume: 42 Pages: 1360-1366
  • Peer Reviewed
• [Journal Article] Pancreatic stellate cells in hypoxia enhance pancreatic cancer invasiveness via secretion of connective tissue growth factor (2013)
  • Author(s): Daiki Eguchi, Naoki Ikenaga, Kenoki Ohuchida, Shingo Kozono, Lin Cui, Fujiwara Kenji, Koji Shindo, Takao Ohtsuka, Shunichi Takahata, Kazuhiro Mizumoto and Masao Tanaka
  • Journal Title: Journal of Surgical Research Volume: 181 Pages: 225-33
  • Peer Reviewed
• [Journal Article] Pirfenidone inhibits desmoplasia of pancreatic cancer by regulating stellate cells (2013)
  • Author(s): Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Ming Zhao, Lin Cui, Koji Shindo, Kazuhiro Mizumoto, and Masao Tanaka
  • Journal Title: Cancer Research Volume: 73 Pages: 2345-56
  • Peer Reviewed
• [Journal Article] Kindlin-2 expression in peritumoral stroma is associated with poor prognosis in pancreatic ductal adenocarcinoma (2013)
  • Author(s): Prawej Mahawithitwong, Kenoki Ohuchida, Naoki Ikenaga, Hayato Fujita, Ming Zhao, Shingo Kozono, Koji Shindo, Takao Ohtsuka, Shinichi Aishima, Kazuhiro Mizumoto, Masao Tanaka
  • Journal Title: Pancreas Volume: 42 Pages: 663-9
  • Peer Reviewed
• [Journal Article] Biological evaluation of protein nanocapsules containing doxorubicin (2013)
  • Author(s): Riki Toita, Masaharu Murata, Kana Abe, Sayoko Narahara, Jing Shu Piao, Jeong-Hun Kang, Kenoki Ohuchida, Makoto Hashizume
  • Journal Title: International Journal of Nanomedicine Volume: 8 Pages: 1989-1999
  • Peer Reviewed
• [Journal Article] Migratory activity of CD105+ pancreatic cancer cells is strongly enhanced by pancreatic stellate cells (2013)
  • Author(s): Kenji Fujiwara, Kenoki Ohuchida, Takao Ohtsuka, Kazuhiro Mizumoto, Koji Shindo, Naoki Ikenaga, Lin Cui, Shunichi Takahata, Shinichi Aishima, and Masao Tanak
  • Journal Title: Pancreas Volume: 42(8) Pages: 1283-90
  • Peer Reviewed
• [Journal Article] S100A4 mRNA expression level is a predictor of radiosensitivity of pancreatic cancer cells (2013)
  • Author(s): Shingo Kozono, Kenoki Ohuchida, Takao Ohtsuka, Lin Cui, Daiki Eguchi, Kenji Fujiwara, Ming Zhao, Kazuhiro Mizumoto, Masao Tanaka
  • Journal Title: Oncology Reports Volume: 30(4) Pages: 1601-8
  • Peer Reviewed
• [Journal Article] MAL2 expression predicts distant metastasis and short survival in pancreatic cancer (2013)
  • Author(s): Daiki Eguchi, Kenoki Ohuchida, Shingo Kozono, Naoki Ikenaga, Koji Shindo, Lin Cui, Kenji Fujiwara, Shin Akagawa, Takao Ohtsuka, Shunichi Takahata, Shoji Tokunaga, Kazuhiro Mizumoto, Masao Tanaka
  • Journal Title: Surgery Volume: 154(3) Pages: 573-82
  • Peer Reviewed
• [Journal Article] Fibroblasts expressing podoplanin enhance the tumor progression of invasive ductal carcinoma of pancreas (2013)
  • Author(s): Shindo Koji, Aishima Shinichi, Ohuchida Kenoki, Fujiwara Kenji, Mizumoto Kazuhiro, Tanaka Masao, Oda Yoshinao
  • Journal Title: Molecular Cancer Volume: 12(1) Pages: 168-168
  • Peer Reviewed
• [Journal Article] 腫瘍内heterogeneity に着目した膵癌個別化治療の可能性 -腫瘍個別化から細胞個別化へ- (2013)
  • Author(s): 大内田研宙, 大塚隆生, 水元一博, 田中雅夫
  • Journal Title: 胆と膵 Volume: Vol.30(2) Pages: 165-9
  • Peer Reviewed
• [Journal Article] Pirfenidone inhibits desmoplasia of pancreatic cancer by regulating stellate cells. (2013)
  • Author(s): Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Ming Zhao, Lin Cui, Koji Shindo, Kazuhiro Mizumoto, and Masao Tanaka
  • Journal Title: Cancer Research Volume: 73 Issue: 7 Pages: 2345-2356
  • DOI: 10.1158/0008-5472.can-12-3180
  • Peer Reviewed
• [Journal Article] Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer (2012)
  • Author(s): Zhao Ming, Tominaga Yohei, Ohuchida Kenoki, Mizumoto Kazuhiro, Cui Lin, Kozono Shingo, Fujita Hayato, Maeyama Ryo, Toma Hiroki, Tanaka Masao
  • Journal Title: Cancer Science Volume: 103(1) Pages: 58-66
  • Peer Reviewed
• [Journal Article] Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages (2012)
  • Author(s): Masaharu Murata, Sayoko Narahara, Kaori Umezaki, Riki Toita, Shigekazu Tabata, Jing Shu Piao, Kana Abe, Jeong-Hun Kang, Kenoki Ohuchida, Lin Cui, Makoto Hashizume
  • Journal Title: International Journal of Nanomedicine Volume: 7 Pages: 4353-62
  • Peer Reviewed
• [Journal Article] Pancreatic cancer cells enhance the ability of collagen internalization via epithelial-mesenchymal transition (2012)
  • Author(s): Naoki Ikenaga, Kenoki Ohuchida, Kazuhiro Mizumoto, Shin Akagawa, Kenji Fujiwara, Daiki Eguchi, Shingo Kozono, Takao Ohtsuka, Shunichi Takahata and Masao Tanaka
  • Journal Title: PLos One Volume: 7(7)
  • Peer Reviewed
• [Journal Article] Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma (2012)
  • Author(s): Kosuke Tsutsumi, Norihiro Sato, Kazuhiro Mizumoto, Katsuya Morimatsu Tadashi Kayashima, Hayato Fujita, Kenoki Ohuchida, Takao Ohtsuka, Shunichi Takahata, Masao Tanaka
  • Journal Title: Annals of Surgical Oncology Volume: 19 Suppl 3
  • Peer Reviewed
• [Journal Article] MicroRNA-10a is Overexpressed in Human Pancreatic Cancer and Involved in its Invasiveness possibly via Suppression of the HOXA1 gene (2012)
  • Author(s): Kenoki Ohuchida, Kazuhiro Mizumoto, Cui Lin, Jun Yu, Hiroshi Yamaguchi, Shunichi Takahata, Takao Ohtsuka, Norihiro Sato, Hiroki Toma, Masafumi Nakamura, Eishi Nagai, Makoto Hashizume, and Masao Tanaka
  • Journal Title: Annals of Surgical Oncology Volume: 19 Pages: 2394-402
  • Peer Reviewed
• [Journal Article] A CD271-positive subpopulation of pancreatic stellate cells is correlated with the prognosis of patients with pancreatic cancer and regulated by interaction with cancer cells (2012)
  • Author(s): Kenji Fujiwara, Kenoki Ohuchida, Kazuhiro Mizumoto, Koji Shindo, Naoki Ikenaga, Shunichi Takahata, Shinichi Aishima, and Masao Tanaka
  • Journal Title: PLoS ONE Volume: 7(12)
  • Peer Reviewed
• [Journal Article] 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 (2011)
  • Author(s): 大内田研宙, 大塚隆生, 水元一博, 田中雅夫
  • Journal Title: 胆と膵 Volume: 32巻9号 Pages: 807-10
  • Peer Reviewed
• [Journal Article] Molecular biology-based diagnosis and therapy for pancreatic cancer (2011)
  • Author(s): Fujita H, Ohuchida K, Mizumoto K, Tanaka M
  • Journal Title: Fukuoka Igaku Zasshi Volume: 102(6) Pages: 203-14
  • NAID: 40018954520
  • Peer Reviewed
• [Journal Article] 膵癌の分子生物学的解析の現状 (2011)
  • Author(s): 大内田研宙, 藤田逸人, 水元一博, 田中雅夫
  • Journal Title: 腫瘍内科 Volume: 7巻2号 Pages: 131-6
  • Peer Reviewed
• [Journal Article] Mass Spectrometry-based Metabolic Profiling of Gemcitabine-sensitive and Gemcitabine-resistant Pancreatic Cancer Cells
  • Author(s): Yoshinori Fujimura, Naoki Ikenaga, Kenoki Ohuchida, Daiki Setoyama, Miho Irie, Daisuke Miura, Hiroyuki Wariishi, Masaharu Murata, Kazuhiro Mizumoto, Makoto Hashizume and Masao Tanaka
  • Journal Title: Pancreas Volume: (in press)
  • Peer Reviewed
• [Presentation] CD166 Expression Characterized Tumorigenicity, and Invasive and Migratory Activities of Pancreatic Cancer Cell Lines, Ammerican Pancreatic Association (2013)
  • Author(s): Fujiwara K, Ohuchida K, Akagawa S, Ohtsuka T, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Expression of Glucagon-like Peptide 1 Recepter and Biological Behavior in Pancreatic Neuroendocrine Tumors, Ammerican Pancreatic Association (2013)
  • Author(s): Cases A.I., Ohtsuka T, Fujino M, Ideno N, Kzono S, Zhao M, Ikenaga N, Ohuchida K, Oda Y, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Clinical significance of GNAS mutation for invasive pancreatic carcinoma distinct from/derived from intraductal papillary mucinous neoplasm(IPMN) of the pancreas , Ammerican Pancreatic Association (2013)
  • Author(s): Ideno N, Ohtsuka T, Tamura K, Aso T, Ohuchida K, Takahata S, Oda Y, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Salinomycin induced Autophagy and is Related with its Killing Effect for Pancreatic Cells Ammerican Pancreatic Association (2013)
  • Author(s): Nakata K, Zhao M, Ohuchida K, Miyasaka Y, Maeyama R, Ohtsuka T, Nagai E, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Treatment Strategy for Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreatic Based on the Assessment of Recurrence in the Remnant Pancreas after Resection : A Retrospective Review. Ammerican Pancreatic Association (2013)
  • Author(s): Tamura K, Ohtsuka T, Ideno N, Aso T, Shindo K, Oda Y, Ohuchida K, Takahata S, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Reduced Anterior Gradient 2 Expression is Induced by EMT and Correlated with Poor Outcome in Pancreatic Ductal Adenocarcinoma Ammerican Pancreatic Association (2013)
  • Author(s): Mizuuchi Y, Aishima S, Ohuchida K, Shindo S, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Histon Deacetylase 1 is Responsible for Radioresistance of Pancreatic Cancer cells Ammerican Pancreatic Association (2013)
  • Author(s): Tanaka T, Ohuchida K, Mizumoto K, Kozono S, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Comparisons of Characteristics of Peritoneal Fibroblasts in Dissemination with those of Mesothelial Cells and Pancreatic Stellate Cells in Pancreatic Cancer Ammerican Pancreatic Association (2013)
  • Author(s): Akagawa S, Ohuchida K, Torada N, Eguchi D, Kozono S, Ohtsuka T, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Clinical Significance of Stromal CD90 and alpha-SMA Expression in Pancreatic Cancer Ammerican Pancreatic Association (2013)
  • Author(s): Sada M, Ohuchida K, Fujiwara K, Horioka K, Tanaka T, Zheng B, Cases A.I., Akagawa S, Shindo K, Ohtsuka T, Takahata S, Oda Y, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting
  • Place of Presentation: Miami
• [Presentation] Regulation of Pancreatic Stellate cells for Treatment of Pancreatic cancer.
  • Author(s): Kenoki Ohuchida
  • Organizer: The 6th International Conference for Treatment of Pancreatic Cancer
  • Place of Presentation: Taiwan
  • Invited