Osteopontin-CD44 pathway confers radioresistance on oral squamous cell carcinoma cells.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24125
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Nakashima Hikaru 熊本大学, 病院, 非常勤診療医師 (20849103)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: Osteopontin / 口腔扁平上皮癌 / 放射線耐性 / CD44

Outline of Final Research Achievements

The frequency of OPN-high patients was significantly higher among the cases who showed poor pathological response to preoperative chemoradiotherapy. OPN play an important role in radioresistance of OSCC cells. Therefore, we examined the mechanism of radiresistance via OPN signaling making use of inhibition representative receptors. Our results showed that radioresistance was canceled by blockade of CD44, and this ability was brought by reducing DNA damage or by defensing from ROS. And GSH concentration was significantly increased in OSCC cells after irradiation, which were added OPN. Furthermore, addition of OPN promoted complex formation of CD44-xCT after irradiation.Thus, it is also suggested that targeting OPN signaling could be a new approach (Sulfasalazine: xCT inhibitor) to overcome radioresistance of OSCC patients.

Free Research Field

口腔扁平上皮癌

Academic Significance and Societal Importance of the Research Achievements

OSCCにおける放射線治療は有効な治療法の一つだが、放射線抵抗性を示す細胞の存在が患者予後を極めて不良にするため、そのメカニズム解明は急務である。今回われわれの研究成果によって、OSCCにおけるOPN-CD44経路を介した放射線耐性機構の解明によって、新たな治療法の開発に繋がる可能性を示した。またその候補としてxCT阻害薬スルファサラジンが挙がるが、同剤は関節リウマチなどに既に承認され高い治療効果を示しており、ドラッグリポジショニングの観点からも臨床応用に期待ができる。したがって同剤を併用した治療法開発は放射線抵抗性OSCCを有する患者へ有望かつ創造性に富む治療法の候補となりうる。