integrated analysis of mechanisms promoting tumorigenesis by adipocyte

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Fujita Health University
• Principal Investigator: Maeda Masao 藤田医科大学, 医学部, 講師 (00769614)
• Co-Investigator(Kenkyū-buntansha): 下野 洋平 藤田医科大学, 医学部, 教授 (90594630) ; 林 孝典 藤田医科大学, 医学部, 講師 (40724315)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脂肪細胞 / がん / 腫瘍間質 / 卵巣がん

Outline of Final Research Achievements

This study elucidated the one of the molecular mechanisms by which adipose tissue promotes cancer formation. Patient-derived tumor xenografts (PDXs) and adipose tissue-derived stem cells (ADSCs) were established from the adipose cell-rich peritoneal tissue collected from surgical specimens of ovarian cancer patients who were given consent. These PDX cells and ADSC cells were co-cultured and analyzed. Using the established ADSC cells, we performed cytokine array and identified several factors secreted by adipocytes. And we attempted to identify existing drugs that target adipose-tumor associations by screening existing drugs using a co-culture system of PDX and ADSC cells. In addition, DPP4 was identified as one of the secreted factors of omental ADSC cells, adipocytes were shown to promote cancer progression via DPP4, and DPP4 inhibitor’s potential as a drug to inhibit the progression of ovarian cancer was demonstrated.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、脂肪細胞がDPP4を介して卵巣がんを進展させることを明らかにし、脂肪細胞の腫瘍間質としての脂肪細胞の学術的意義をより強固なものにできたと考えられた。また、既存の薬剤であるDPP4阻害剤が脂肪細胞による卵巣がん進展を抑制する可能性を示せたことは社会的意義が大きいと考えられた。今後、腫瘍間質である脂肪細胞を標的とした新たながんの治療法開発につなげたいと考えている。