Analysis about stemness and pathophysiology of pancreatic cancer stem cells expressing calreticulin

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16365
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Yamaguchi University
• Principal Investigator: MATSUKUMA Satoshi 山口大学, 医学部附属病院, 助教 (10634743)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 膵癌幹細胞 / Calreticulin / 癌幹細胞性

Outline of Final Research Achievements

Panc-1 Lm, a pancreatic cancer stem-like cell enriched population induced from the pancreatic cancer cell line Panc-1, has a high proportion of side population showing an increased ABC transporter activity as a mechanism of drug resistance, and has a sphere-forming ability. These results implied that Panc-1 Lm has cancer stem cell properties. And, their high expression of PD-L1, which is an immune checkpoint-related molecule, and reduced expression of HLA class I molecule could be a mechanism of evasion from the immune surveillance. Moreover, Calreticulin-positive cells contained in the induced cells had higher sphere-forming ability and immune escape mechanism by surface antigens.

Free Research Field

癌幹細胞

Academic Significance and Societal Importance of the Research Achievements

本研究を通して、我々が独自の方法で、膵癌細胞株から誘導した膵癌幹細胞様細胞が豊富な細胞集団の癌幹細胞性が確認できた。さらに、この細胞は免疫チェックポイント関連分子を発現し、HLA class I分子の発現を低下させることで、免疫監視機構から逃避している可能性が示唆された。今後、表面抗原のみならず免疫逃避に関連する液性因子の発現の解析、免疫担当細胞との共培養実験を通して、癌幹細胞の免疫逃避機構を解明することで、癌の新たな治療法開発を目指している。