New strategy for pancreatic cancer treatment by regulating pancreatic stellate cell activation through autophagy

• Project/Area Number: 17H06942
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: ENDO Sho 九州大学, 医学研究院, 共同研究員 (20801749)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 膵癌 / オートファジー / 癌間質相互作用 / 膵癌細胞 / 膵星細胞 / 膵臓癌

Outline of Final Research Achievements

Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor microenvironment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated in cancer stroma. We previously reported that autophagy played an important role for the activation of PSCs and its inhibition led to reduce tumor progression and metastasis. In this study, we established pancreatic stellate cells derived from pancreatic cancer and non-pancreatic cancer lesions, and confirmed the difference between these autophagy activities. In addition, we comprehensively analyzed mRNA expression in these pancreatic stellate cells and selected several candidate genes that could be autophagy related genes. These results might be a new strategy for pancreatic cancer treatment.

Academic Significance and Societal Importance of the Research Achievements

膵癌は発見時に既に治癒切除が困難であることが多く、さらに放射線照射や化学療法に抵抗性であるという特徴をもつ。このため、膵癌患者の5 年生存率はここ30 年でほとんど改善なく、治療法の開発は社会的緊急性・重要性が高い。膵星細胞は癌間質中で活性化し、その活性化が膵癌の増殖・転移を促進することは明らかであるが、活性化を誘導する詳細な機序は未だ解明されておらず、この機序の解明は膵癌に対する新たな治療開発につながることが期待される。

Research Products

• [Journal Article] CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis. (2019)
  • Author(s): Yan Z, Ohuchida K, Zheng B, Okumura T, Takesue S, Nakayama H, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M
  • Journal Title: J Cancer Res Clin Oncol. Volume: 145 Issue: 5 Pages: 1147-1164
  • DOI: 10.1007/s00432-019-02860-z
  • Peer Reviewed / Open Access
• [Journal Article] Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix (2018)
  • Author(s): Okumura T, Ohuchida K, Kibe S, Iwamoto C, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Sada M, Horioka K, Mochidome N, Arita M, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M
  • Journal Title: Int J Cancer Volume: 144 Issue: 6 Pages: 1401-1413
  • DOI: 10.1002/ijc.31775
  • Peer Reviewed / Open Access
• [Presentation] オートファジー抑制は、サリノマイシンによる膵癌細胞増殖抑制効果を増強する (2018)
  • Author(s): 相良亜希子、仲田興平、遠藤翔、米永晃子、安藤陽平、岐部晋、中山宏道、武居晋、進藤幸治、森山大樹、宮坂義浩、大内田研宙、大塚隆生、水元一博、中村雅史
  • Organizer: 第49回日本膵臓学会大会
• [Presentation] CD110の阻害は、マウスの膵癌肝転移を抑制する (2018)
  • Author(s): 厳子龍、大内田研宙、森山大樹、仲田興平、宮坂義浩、永井俊太郎、大塚隆生、中村雅史
  • Organizer: 第77回日本癌学会学術総会
• [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