To elucidate distribution heterogeneity in cancer microenvironment of variable DDS using KPCL mice and its modification.

• Project/Area Number: 17K16563
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: EGUCHI Daiki 九州大学, 医学研究院, 共同研究員 (90726390)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膵癌 / 微小環境 / DDS / ナノ粒子 / KPCL / 腫瘍微小環境 / 膵癌自然発生マウスモデル / drug delivery system

Outline of Final Research Achievements

We created a variable drug delivery system (DDS) using nano particles and analyzed its distribution in the tumor microenvironment of genetically engineered spontaneous pancreatic carcinogenic model mice with luciferase (KPCL mice). Our variable nano system consisted of heat shock protein conjugated with gadolinium contrast agent for magnetic resonance imaging and could change its size easily. The Distribution and accumulation of the DDS in tumors varied depending on its size. We found the best size of DDS and it capable of penetrate stromal tissue. These results suggest that our DDS has a promising potential not only as contrast agent but as career of therapeutic agent and may improve prognosis of pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究は治療抵抗性の高い膵癌における有望な治療戦略の一つであるドラッグデリバリーシステム（DDS）に関して、特に腫瘍微小環境を含めた腫瘍内分布を解析し、DDSの可変性を利用して腫瘍内分布の不均一性を改善して治療効果を向上させることを目的として行った。膵癌自然発癌マウスを用いた実験結果から、より効果的なDDSのサイズを見出すことができ、またDDSが膵癌の治療抵抗性の主な原因の一つである豊富な間質を貫いて腫瘍に到達していることが確認できた。これらの結果から、このDDSを治療薬に用いることで膵癌の治療成績向上が期待できる。

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] 膵星細胞が誘導する新たな膵癌局所微小浸潤機序の解明 (2017)
  • Author(s): 肥川和寛、大内田研宙、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25回日本消化器関連学会週間 第15回日本消化器外科学会大会
• [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