Development of novel pancreatic cancer treatment strategy targeting the pancreatic cancer stroma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18076
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Hirosaki University
• Principal Investigator: Nagase Hayato 弘前大学, 医学部附属病院, 助教 (10750862)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 膵癌 / 間質 / ヒアルロン酸 / 化学療法

Outline of Final Research Achievements

4-methylumbelliferone (MU) did not affect the expression of hyaluronan (HA) receptors, CD44 and RHAMM, in pancreatic cancer cells, suggesting that MU may exert its antitumor effect by decreasing pericellular HA and suppressing intracellular signaling by binding of HA to its receptors. receptor binding, suggesting that MU may exert its anti-tumor effect by reducing pericellular hyaluronan. In addition, γδT cells were isolated and cultured from healthy human subjects, and their cytotoxic activity against pancreatic cancer cells was examined, and the cytotoxicity was enhanced when they were used in combination with MU. In addition, experiments using immunodeficient mice transplanted with human pancreatic cancer cells confirmed the anti-tumor effects of MU (tumor shrinkage, improved survival rate, increased concentration of anti-cancer drugs in tumor tissue, and accelerated invasion of γδT cells into the tumor).

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究はMUが他の抗癌剤の作用を増強するchemosensitizerとしての有用性を実証するものである。膵癌に対する化学療法のKey DrugであるNab-PaclitaxelとMUを併用することによって治療成績が向上する可能性があり、本研究を継続することにより実証可能である。また、現時点で効果が実証されていない免疫療法においても、MUと併用することで腫瘍学的効果が得られる可能性があると考える。