Development of head and neck cancer treatment targeting HIF1-alpha

Research Project

Project/Area Number	17K11410
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Otorhinolaryngology
Research Institution	Keio University
Principal Investigator	OZAWA Hiroyuki 慶應義塾大学, 医学部(信濃町), 講師 (30327621)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	低酸素応答因子 / ANGPTL4 / 中咽頭癌 / 下咽頭癌 / 頭頸部癌 / 転移 / 低酸素誘導因子
Outline of Final Research Achievements	We investigated the association of ANGPTL4, one of the HIF1-α transcription factors, with head and neck cancer. We examined the immunohistological expression of ANGPTL4 in hypopharyngeal carcinoma cases and its association with clinical data. Multivariate analysis revealed that ANGPTL4 expression was an independent prognostic determinant for overall survival. Similar results were obtained for oropharyngeal carcinoma patients. Subsequent knockdown of ANGPTL4 expression in head and neck cancer cell lines showed that the down-regulation of ANGPTL4 reduced the expression of EMT-associated genes and genes associated with cancer stem cell properties. These results indicated that ANGPTL4 has a possibility to act as a tumor suppressor in head and neck cancers, although ANGPTL4 has been reported to be involved in both tumor promotion and suppression.
Academic Significance and Societal Importance of the Research Achievements	頭頸部癌全体の生存率は50％程度に過ぎず、予後を改善するためには予後因子の1つである転移を抑制する治療手段を確立すること、治療抵抗性である転移巣への治療効果を改善する必要がある。今回の検討により、HIF1-αの転写因子であるANGPTL4が頭頸部癌において腫瘍抑制に関わることが示された。ANGPTL4を制御する薬は臨床レベルでは存在しないが、発現を促進する薬剤を開発することにより、将来の頭頸部癌の治療薬として期待できる。また2種の癌種で予後規定因子となっていたことから、ANGPTL4発現が予後予測などのバイオマーカーとして活用できる可能性が示された。