Clarification and regulation of the involvement between BM-derived cells and pancreatic cancer clonality

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16366
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: Chika Iwamoto 九州大学, 大学病院, 特任助教 (10752842)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膵癌 / 浸潤

Outline of Final Research Achievements

In pancreatic ductal adenocarcinoma (PDAC), mesenchymal stem cells-derived tumor stroma seems to promote tumor development. However, involvement of bone marrow (BM)-derived cells on tumor progression and its mechanism remains unclear. We aimed to investigate an association between pancreatic cancer progression and BM-derived cells. In the pancreas of allogeneic models, GFP+BM-derived immune cells were accumulated at invasive front, and a few GFP+aSMA+ cells were detected. Some BM-derived cells interacted with pancreatic cancer cells (PCCs) expressed CAF markers. The heterogeneity of PCCs for PDAC development was investigated using whole exome sequencing. We identified the several organ-specific mutations.

Free Research Field

腫瘍免疫学、分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

膵癌細胞の刺激により骨髄由来細胞がCAFマーカーを発現することを新たに見出したことで、CAF のsubsetには様々な由来細胞が存在することが示唆された。由来細胞の同定は、膵癌微小環境におけるCAFの役割をより理解するためには必要不可欠であることから、本研究結果は学術的意義が高いと言える。また、転移形成において、臓器特異的な遺伝子変異が見られることが示唆された。臓器特異的転移形成の機序を解明することで、新たな治療法の開発に役立つと考えられる。これは、膵癌のみならず転移形成を生じる他の癌腫の治療にも応用できる可能性を秘めているため、社会的意義は大きいと言える。