THE INFLUENCE OF SENESCENT STROMA ON PDAC

• Project/Area Number: 17K10693
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: Ohta Tetsuo 金沢大学, 医学系, 教授 (40194170)
• Co-Investigator(Kenkyū-buntansha): 宮下 知治 金沢大学, 医学系, 協力研究員 (30397210)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膵癌 / 細胞老化 / SASP / 血管外血小板 / Podoplanin / 間質 / 微小環境 / 癌

Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive desmoplastic stroma. It is known that senescent cancer stroma affects cancer progression through the senescence-associated secretory phenotype (SASP). Our aims is to assess whether SASP factor expression is associated with the prognosis of patients with PDAC. To examine the expression and localization of senescent stromal cells, we carried out an immunohistochemical analysis using anti- p16 and IL-6 antibodies. IL-6 expression was detected with the intensity being weak in 36 and strong in 29 specimens. Patients with strong IL-6 expression had significantly lower overall survival rates than those with weak IL-6 expression. The intensity of stromal IL-6 expression was also correlated positively to the stromal p16 expression at the same area. The association of IL-6 expression with clinical outcomes provide us with an understanding of the effect of senescent stroma on the prognosis of PDAC.

Academic Significance and Societal Importance of the Research Achievements

本研究では、膵癌組織内で構築される薬剤抵抗性・免疫寛容状態と腫瘍の増殖・進展に関わる細胞間相互作用の分子基盤を、癌間質内での腫瘍関連線維芽細胞における細胞老化とSASP因子という視点から解明し、新規治療法開発の可能性が示唆された。

Research Products

• [Presentation] PANCREATIC SENESCENT STROMA INFLUENCE ON PROGNOSIS IN PDAC (2019)
  • Author(s): Yuto Kitano, Tomoharu Miyashita, Tetsuo Ohta
  • Organizer: DDW2019
  • Int'l Joint Research