Role of adipose tissue in pancreatic cancer local invasion as a component of tumor microenvironment

• Project/Area Number: 15K10187
• 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: TOMA Hiroki 九州大学, 医学研究院, 共同研究員 (80437780)
• 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): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 脂肪組織由来幹細胞 / 癌関連線維芽細胞 / 活性化型膵星細胞 / High fat diet / 脂肪酸 / リノレン酸 / S100A4 / 膵周囲脂肪組織

Outline of Final Research Achievements

KPC mice fed a high fat diet had significantly lager visceral fat, primary pancreatic tumors and higher rate of distant organ metastasis than control group. In vitro 3D fat invasion model, pancreatic cancer showed more elongated shape and promoted adjacent tissue fibrosis. Adipose tissue-derived conditioned medium which contains fatty acid enhanced pancreatic cancer cell migration, invasion and increased the numbers of lipid droplets in its cytoplasm. Indirect co-culture of mature adipocytes with cancer cells resulted in adipocyte shrinkage, while elevating the concentration of fatty acids in the medium.

Research Products

• [Journal Article] Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo180 (2018)
  • Author(s): Koikawa K, Ohuchida K, Takesue S, Ando Y, Kibe S, Nakayama H, Endo S, Abe T, Okumura T, Horioka K, Sada M, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Ohuchida R, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
  • Journal Title: Cancer Letters Volume: 412 Pages: 143-154
  • DOI: 10.1016/j.canlet.2017.10.010
  • Peer Reviewed / Open Access
• [Presentation] 膵癌における膵周囲脂肪組織線維化と脂肪組織由来幹細胞の役割 (2017)
  • Author(s): 奥村隆志、大内田研宙、安藤陽平、岐部晋、武居晋、中山宏道、阿部俊也、遠藤翔、肥川和寛、厳子龍、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] 脂肪組織由来幹細胞は膵癌における癌関連線維芽細胞の供給源となり腫瘍形成を促進する (2017)
  • Author(s): 肥川和寛、奥村隆志、大内田研宙、岐部晋、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48回日本膵臓学会大会
• [Presentation] Fatty acid uptake via CD36 enhances invasiveness of pancreatic cancer cells. (2016)
  • Author(s): Okumura T, Ohuchida K, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Nakamura M
  • Organizer: The 47th Annual meeting of American Pancreatic Association
  • Place of Presentation: Boston(USA)
  • Year and Date: 2016-10-28
  • Int'l Joint Research
• [Presentation] Peripancreatic adipose tissue inhibits the proliferation of pancreatic cancer cells and contributes chemoresistance. (2016)
  • Author(s): Okumura T, Ohuchida K, Abe T, Endo S, Koikawa K, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Nakamura M
  • Organizer: Joint Meeting of the IAP / JPS / AOPA 2016
  • Place of Presentation: Sendai(JAPAN)
  • Year and Date: 2016-08-06
  • Int'l Joint Research
• [Presentation] 膵周囲脂肪細胞から放出された遊離脂肪酸は膵癌細胞に取り込まれ、遊走・浸潤能を増強する (2016)
  • Author(s): 奥村隆志
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: アスティ徳島(徳島市）
  • Year and Date: 2016-07-15
• [Presentation] 膵周囲脂肪組織は肝癌細胞の遊走・浸潤機能を増強し、局所浸潤に関与する (2016)
  • Author(s): 奥村隆志、大内田研宙、武居晋、中山宏道、阿部俊也、遠藤翔、肥川和寛、千々岩芳朗、吉田真樹、鄭彪、佐田政史、堀岡宏平、森山大樹、三好圭、宮坂義浩、真鍋達也、大塚隆生、植木隆、永井英司、水元一博、中村雅史
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: リーガロイヤルホテル大阪(大阪市）
  • Year and Date: 2016-04-14
• [Presentation] 脂肪組織由来幹細胞は膵癌細胞の遊走・浸潤を促進し悪性度に関与する (2015)
  • Author(s): 奥村隆志、大内田研宙、阿部俊也、遠藤翔、肥川和寛、千々岩芳朗、吉田真樹、佐田政史、堀岡宏平、真鍋達也、大塚隆生、高畑俊一、植木隆、永井英司、水元一博、中村雅史、田中雅夫
  • Organizer: JDDW2015 第23回消化器関連学会週間
  • Place of Presentation: 東京都
  • Year and Date: 2015-10-08