Reproduction of the three dimensional coculture model reflecting pancreatic cancer microenvironment and metabolic analysis for the stromal remodeling by MALDI Mass-spectrometry Imaging.

• Project/Area Number: 16K10598
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: SAKAI Hiroshi 九州大学, 医学研究院, 共同研究員 (80611665)
• Co-Investigator(Kenkyū-buntansha): 水元 一博 九州大学, 大学病院, 准教授 (90253418) ; 大内田 研宙 九州大学, 大学病院, 講師 (20452708)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: MALDI-MSI / Energy Charge / 凍結組織アレイ / バイオマーカー検索 / バイオマーカー探索 / 膵癌 / 癌微小環境 / 癌間質相互作用 / 膵オルガノイド

Outline of Final Research Achievements

In the present study, metabolite analysis was performed by MALDI-MSI on pancreatic cancer tissues and pancreatic cancer microenvironment reproduction models. We tried to detect metabolites specific to cancer - stromal interaction and stromal remodeling. The three-dimensional co-culture system clarified the mechanism of pancreatic stellate cells remodeling the stroma by Endo 180. In addition, for performing MALDI-MSI on frozen sections, we developed pancreatic cancer organoid models reflecting the tumor microenvironment derived from human pancreatic cancer. From now on, we will perform metabolome mapping by MALDI-MSI using the model, and continue to search for metabolites characteristic of the stromal remodeling.

Academic Significance and Societal Importance of the Research Achievements

従来の質量分析法では、代謝物の抽出・濃縮が不可欠で組織内局在情報が失われてしまうが、マトリックス支援レーザー脱離イオン化質量分析イメージング（MALDI-MSI）を用いることで、メタボローム情報を組織上にマッピングすることが可能となった。本研究は、膵癌組織および3次元培養モデルに対するMALDI-MSIを用いた代謝物解析、間質リモデリングに特徴的な因子の同定を行った。膵癌組織に特徴的な代謝産物を同定し、そのメカニズムを明らかにすることによって早期診断・新規治療法確立の手がかりを探ることにつながると考えられる。

Research Products

• [Journal Article] Visualizing Energy Charge in Breast Carcinoma Tissues by MALDI Mass-spectrometry Imaging Profiles of Low-molecular-weight Metabolites (2018)
  • Author(s): TORATA NOBUHIRO、KUBO MAKOTO、MIURA DAISUKE、OHUCHIDA KENOKI、MIZUUCHI YUSUKE、FUJIMURA YOSHINORI、HAYAKAWA EISUKE、KAI MASAYA、ODA YOSHINAO、MIZUMOTO KAZUHIRO、HASHIZUME MAKOTO、NAKAMURA MASAFUMI
  • Journal Title: Anticancer Research Volume: 38 Issue: 7 Pages: 4267-4272
  • DOI: 10.21873/anticanres.12723
  • Peer Reviewed
• [Journal Article] Degree of desmoplasia in metastatic lymph node lesions is associated with lesion size and poor prognosis in pancreatic cancer patients (2017)
  • Author(s): Nakayama H, Ohuchida K, Yoshida M, Miyazaki T, Takesue S, Abe T, Endo S, Koikawa K, Okumura T, Moriyama T, Nakata K, Miyasaka Y, Shirahane K, Manabe T, Ohtsuka T, Toma H, Tominaga Y, Nagai E, Mizumoto K, Oda Y, Nakamura M.
  • Journal Title: Oncology Letters Volume: 14 Issue: 3 Pages: 3141-3147
  • DOI: 10.3892/ol.2017.6549
  • Peer Reviewed
• [Journal Article] Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells (2017)
  • Author(s): Endo Sho、Nakata Kohei、Sagara Akiko、Koikawa Kazuhiro、Ando Yohei、Kibe Shin、Takesue Shin、Nakayama Hiromichi、Abe Toshiya、Okumura Takashi、Moriyama Taiki、Miyasaka Yoshihiro、Ohuchida Kenoki、Ohtsuka Takao、Mizumoto Kazuhiro、Nakamura Masafumi
  • Journal Title: Pancreatology Volume: 17 Issue: 6 Pages: 990-996
  • DOI: 10.1016/j.pan.2017.08.009
  • Peer Reviewed
• [Presentation] Oxaliplatin投与後の直腸癌組織における蛍光X線分析を用いた金属元素の分布測定 (2018)
  • Author(s): 木庭遼、植木隆、西堀麻衣子、石田竜弘、永吉絹子、貞苅良彦、藤田逸人、永井俊太郎、大内田研宙、大塚隆生、中村雅史
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 放射光蛍光X線分析による白金錯体系薬剤の直腸癌組織内分布の可視化 (2018)
  • Author(s): 木庭遼、永吉絹子、貞苅良彦、藤田逸人、永井俊太郎、大内田研宙、大塚隆生、西堀麻衣子、植木隆、石田竜弘、中村雅史
  • Organizer: 第56回日本癌治療学会学術集会
• [Presentation] Endo180 Expression and Histologic Categorization in Cancer Stroma is an Independent Prognostic Index in Pancreatic Cancer. (2018)
  • Author(s): Koikawa K, Ohuchida K, Yonenaga A, Sagara A, Ando Y, Kibe S, Takesue S,Nakayama H, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: 49th Annual Meeting of the APA
  • Int'l Joint Research
• [Presentation] Basement membrane destruction by pancreatic stellate cells leads to local invasion in pancreatic ductal adenocarcinoma (2018)
  • Author(s): Koikawa K, Ohuchida K, Ando Y, Kibe S, Nakayama H, Takesue S, Endo S, Abe T, Okumura T, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M
  • Organizer: Pancreas 2018
  • Int'l Joint Research
• [Presentation] 癌関連腹膜中皮細胞は膵癌腹膜播腫形成を促進する (2017)
  • Author(s): 阿部俊也、大内田研宙、肥川和寛、遠藤翔、奥村隆志、森山大樹、仲田興平、宮坂義浩、真鍋達也、大塚隆生、永井英司、水元一博、中村雅史
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] マウスモデルを用いた膵癌微小転移形成機序の解析 (2017)
  • Author(s): 武居晋、大内田研宙、安藤陽平、岐部晋、中山宏道、阿部俊也、肥川和寛、遠藤翔、厳子龍、奥村隆志、仲田興平、森山大樹、宮坂義浩、真鍋達也、大塚隆生、永井英司、水元一博、中村雅史
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] Pancreatic organoids elucidate the new mechanisms of pancreatic cancer local invasion. (2017)
  • Author(s): Koikawa K, Ohuchida K, Ando Y, Kibe S, Nakayama H, Takesue S, Yan Z, Abe T, Okumura T, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Okabe Y, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: The 48th Annual Meeting of The American Pancreatic Association
  • Int'l Joint Research
• [Presentation] Adipose Tissue Derived Stromal Cells Accelerate Tumor Progression and Desmoplasia of Pancreatic Cancer (2017)
  • Author(s): Okumura T, Ohuchida K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Nakamura M
  • Organizer: The 48th Annual Meeting of The American Pancreatic Association
  • Int'l Joint Research