Elucidation of complex microenvironmental crosstalk between pancreatic cancer progression and obesity

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17407
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nagoya City University
• Principal Investigator: Nishigaki Ruriko 名古屋市立大学, 医薬学総合研究院(医学), 臨床研究医 (60835164)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 膵癌 / 肥満 / 脂肪細胞

Outline of Final Research Achievements

Visceral adipocytes cell lines were established from lean (L-Adv) and obese mice (O-Adv). Conditioned media from O-Adv significantly increased PDAC cell growth and migration and angiogenic capacity in both human and mice cells,compared to conditioned media from L-Adv. Blocking osteopontin (OPN) in O-Adv canceled O-Adv-induced effects through suppressing AKT phosphorylation and VEGFA expression.In the xenograft model, PDAC tumor volume was significantly increased in obese mice compared with lean mice, whereas blocking OPN significantly inhibited obesity-accelerated tumor growth. In PDAC patients with obesity, high OPN expression in adipose tissues was significantly associated with poor prognosis. In conclusion, obese adipocytes trigger aggressive transformation in PDAC cells to induce PDAC progression and accelerate angiogenesis via OPN secretion.

Free Research Field

消化器病

Academic Significance and Societal Importance of the Research Achievements

過去の複数の疫学的研究により、肥満は膵癌のリスク因子であること、予後不良因子であることがわかっているが、そのメカニズムは不明である。本研究では、細胞実験・動物実験・ヒトの膵癌組織を使用し多角的に検討をおこない、肥満患者の脂肪細胞ではオステオポンチンが高発現し、血管新生を促進し膵癌細胞を悪性化へと誘導するという新たな知見をえた。今後の肥満関連の治療開発や膵癌予防への発展が期待される。