Novel development of individualized treatment strategy in artificial viral therapy targeting modification cancer stroma

• Project/Area Number: 26861084
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: YASUI Takaharu 九州大学, 医学(系)研究科(研究院), 共同研究員 (60611283)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 膵癌 / 膵星細胞 / 細胞外マトリックス / 人工ウイルス

Outline of Final Research Achievements

In pancreatic cancer, cancer microenvironment composed of fibroblasts and extracellular matrix play an important role in invasion, metastasis, and anti-cancer drug resistance. We studied qualitative characteristics of pancreatic cancer stroma that have been focused on quantitative features, and investigated how the impact of this qualitative change on pancreatic cancer.
We found the possibility that extracellular matrix, formed by pancreatic stellate cells, promote the epithelial-mesenchymal transition of pancreatic cancer cells. Further, we reported in the original papers that hypoxia promoted the migration of pancreatic cancer cells through the remodeling of extracellular matrix produced by pancreatic stellate cells. In addition, we announced at domestic and international scientific meeting that pancreatic stellate cells perform remodeling of the extracellular matrix, and that can enhanced invasion of cancer cells by remodeling the arrangement of collagen fiber.

Research Products

• [Journal Article] Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility (2016)
  • Author(s): Sada M, Ohuchida K, Horioka K, Okumura T, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Nakamura M
  • Journal Title: Cancer Lett. Volume: 372 Issue: 2 Pages: 210-218
  • DOI: 10.1016/j.canlet.2016.01.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer (2016)
  • Author(s): Horioka K, Ohuchida K, Sada M, Zheng B, Moriyama T, Fujita H, Manabe T, Ohtsuka T, Shimamoto M, Miyazaki T, Mizumoto K, Oda Y, Nakamura M.
  • Journal Title: Int J Oncol Volume: 48 Issue: 4 Pages: 1499-1508
  • DOI: 10.3892/ijo.2016.3374
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression. (2015)
  • Author(s): Zheng B, ohuchida K, Chijiiwa Y, Zhao M, Mizuuchi Y, Cui L, Horioka K, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M, Tanaka M
  • Journal Title: Mol Carcinog Volume: - Issue: 11 Pages: 1560-1572
  • DOI: 10.1002/mc.22409
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 膵癌の浸潤・転移における癌微小環境の新たな役割 (2015)
  • Author(s): 大内田研宙、大塚隆生、橋爪誠、中村雅史
  • Journal Title: 胆と膵 Volume: 36 Pages: 1181-1187
• [Presentation] Pancreatic Stellate Cells Lead and Promote the Local Invasion of Cancer Cells, by Physically Remodeling the Extracellular Matrix with Collagen Fiber Alignment in Pancreatic Cancer (2015)
  • Author(s): Koikawa K, Ohuchida K, Sada M, Abe T, Endo S, Horioka K, Moriyama T, Miyasaka Y, Ohtsuka T, Ohuchida R, Ueki T, Nagai E, Mizumoto K, Nakamura M
  • Organizer: American Pancreatic Association 46th Annual Meeting
  • Place of Presentation: San Diego(USA)
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] Suppression of CD51 in Pancreatic Stellate Cells Inhibits Tumor Growth by Reducing Stroma and Altering Tumor-Stromal Interaction in Pancreatic Cancer (2015)
  • Author(s): Horioka K, Ohuchida K, Sada M, Zheng B, Ohtsuka T, Ueki T, Nagai E, Mizumoto K, Oda Y, Nakamura M
  • Organizer: American Pancreatic Association 46th Annual Meeting
  • Place of Presentation: San Diego(USA)
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] 低酸素誘導性LOXによる癌間質リモデリングが膵癌浸潤能に与える影響の検討 (2015)
  • Author(s): 佐田政史、大内田研宙、阿部俊也、遠藤翔、肥川和寛、奥村隆志、千々岩芳朗、吉田真樹、堀岡宏平、水内祐介、宮坂義浩、眞鍋達也、大塚隆生、高畑俊一、植木隆、 永井英司、水元一博、小田義直、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
• [Presentation] 膵癌細胞の浸潤機序-浸潤を先導するleading cellsの同定・解析- (2015)
  • Author(s): 肥川和寛、佐田政史、大内田研宙、阿部俊也、遠藤翔、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
• [Presentation] 低酸素誘導性LOXによる癌間質リモデリングが膵癌膵癌浸潤能に与える影響の検討 (2015)
  • Author(s): 佐田政史、大内田研宙、阿部俊也、遠藤翔、肥川和寛、奥村隆志、千々岩芳朗、吉田真樹、堀岡宏平、水内祐介、宮坂義浩、真鍋達也、大塚隆生、高畑俊一、植木隆、永井英司、水元一博、小田義直、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
• [Presentation] 低酸素環境下膵星細胞はPLOD2誘導性間質リモデリングによって膵癌の浸潤を促進する (2015)
  • Author(s): 佐田政史、大内田研宙、奥村隆志、千々岩芳朗、吉田真樹、田中友晴、堀岡宏平、鄭彪、水内祐介、藤原謙次、森山大樹、宮坂義浩、大塚隆生、高畑俊一、小田義直、水元一博、田中雅夫
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-16