The relationship between cancer-associted fibroblast and mast cell on the osteolysis of cancer induced bone disease

Research Project

Project/Area Number	17H04405
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Surgical dentistry
Research Institution	Okayama University
Principal Investigator	Sasaki Akira 岡山大学, 医歯薬学総合研究科, 教授 (00170663)
Co-Investigator(Kenkyū-buntansha)	岸本晃治岡山大学, 医歯薬学総合研究科, 助教 (40243480) 志茂剛北海道医療大学, 歯学部, 教授 (40362991) 奥井達雄岡山大学, 大学病院, 助教 (40610928) 吉岡徳枝岡山大学, 医歯薬学総合研究科, 助教 (50362984) 伊原木聰一郎岡山大学, 医歯薬学総合研究科, 准教授 (80549866)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000) Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2017: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords	マスト細胞 / 癌骨破壊病変 / 癌関連線維芽細胞 / 血管新生 / 口腔扁平上皮癌 / 破骨細胞 / 骨浸潤 / ケミカルメディエーター / 骨破壊病変 / 骨吸収機構 / ケミカルメディエータ－
Outline of Final Research Achievements	Osteoclastic bone resorption plays an important role in bone invasion of cancer and bone destruction of bone metastases. Cancer-associated fibroblasts (B-CAF) present in the bone microenvironment of cancer bone-destructive lesion play an important role in the mechanism. On the other hand, mast cells, which are immune cells, are known to perform various functions such as angiogenesis of cancer, matrix degradation, and production of inflammatory substances related to pain. In this study, we investigated the mechanism of bone destruction by the interaction between B-CAF and mast cells. As a result, mast cells are induced in the cancer bone microenvironment, and their production factors not only directly promote osteoclastogenic bone resorption, but also induce bone resorption, matrix degradation, angiogenesis, etc. for B-CAF. It was suggested to be involved in bone destruction through facilitation and interaction.
Academic Significance and Societal Importance of the Research Achievements	現有の骨破壊病変に対する骨吸収阻害薬は顎骨壊死を誘発する問題があり，新たな戦略が必要である。マスト細胞が癌の進展や血管新生に関わることは知られているが，癌の骨破壊における癌関連線維芽細胞（B-CAF）とマスト細胞の相互機構に注目した報告は殆どない。研究成果は，B-CAFを標的とした新規治療の開発であり，骨微小環境でのマスト細胞の役割や局所環境でのB-CAFの応答遺伝子の探索は創薬研究の基盤となる。