Analysis of cancer promoting action of C5a-C5a receptor system and its application to targeted therapy in oral cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11879
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: OGI HIDENAO 熊本大学, 病院, 非常勤診療医師 (10315426)
• Co-Investigator(Kenkyū-buntansha): 今村 隆寿 熊本大学, 大学院生命科学研究部(医), 准教授 (20176499) ; 田中 拓也 熊本大学, 病院, 非常勤診療医師 (30631767)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: C5a-C5a受容体経路 / 舌癌 / 腺様嚢胞癌

Outline of Final Research Achievements

Cancer cell C5a-receptor (C5aR) expression in one forth to third of tongue or adenoid cystic carcinoma cases indicated an association of the C5a-C5aR system with human oral cancers. C5a generated in the mouse skin site through the activation of the complement system triggered by the immune complexes enhanced invasion and tumor formation of C5aR-positive mouse cancer cells inoculated into the site and recruited myeloid-derived suppressor cells that suppress the anti-tumor immune responses. Inhibition of the cancer promoting effects of C5a by a C5aR antagonist suggested an availability of the therapy targeting the C5a-C5aR system.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

口腔癌には手術以外に放射線、抗癌剤による治療が行われるが、これらの治療法は特異性が低く嚥下障害等の様々な合併症を起こし患者の日常生活に大きな支障をもたらす。今回の研究で解明した癌細胞のC5a受容体発現と内因性C5aによる癌促進はC5a-C5a受容体経路を標的とした新規の癌治療法の有効性を示す。抗C5a受容体抗体やC5a受容体拮抗剤はこの経路を特異的に遮断するので、侵襲や合併症の少ない治療法として期待される。