Investigation of the mechanism of anti-tumor activity by Secretoglobin (SCGB) 3A2.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20813
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Tohoku University
• Principal Investigator: Nakayama Shun 東北大学, 医学系研究科, 大学院非常勤講師 (30968110)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: pancreatic cancer / CAFs / SCGB3A2

Outline of Final Research Achievements

We hypothesized that SCGB3A2 induces STAT1 activation in pancreatic cancer CAFs via an IFNAR-mediated pathway. We established cell lines by isolation and culture of CAFs from 5 pancreatic cancer surgical specimens and immortalized them. We generated IFNAR1 knockdown cell lines using shRNA in patient-derived CAFs and created an orthotopic xenograft model in which patient-derived CAFs were transplanted orthotopically with a pancreatic cancer cell line (AsPC-1) in NOG mice. We are currently in the process of generating SCGB3A2 protein, which will be administered to these knockdown and mouse models to verify the association between the anti-tumor effects of SCGB3A2 and IFNAR.

Free Research Field

Cancer research

Academic Significance and Societal Importance of the Research Achievements

生体内で肺発生における成長因子様作用、肺線維症における抗線維化作用、アレルギー性気道炎症に対する抗炎症作用など多彩な作用をもつサイトカイン様蛋白Secretoglobin (SCGB) 3A2は主に肺に特異的に発現する蛋白であり、肺腺癌においては抗腫瘍作用を有することが確認されているが、その機序については明らかになってはいない。
本研究は、消化器癌で最も難治性である膵癌において特に癌微小環境におけるSCGB3A2の作用を解明することで、新規治療薬として利用できる可能性を検証する足がかりとなった。