2020 Fiscal Year Final Research Report

The promotion effect of 27-hydroxycholesterol as selective estrogen receptor modulator on the proliferation of lung cancer

Research Project

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Project/Area Number	18K08800
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55040:Respiratory surgery-related
Research Institution	Tokyo Medical University
Principal Investigator	Furukawa Kinya 東京医科大学, 医学部, 教授 (20246292)
Co-Investigator(Kenkyū-buntansha)	本多彰東京医科大学, 医学部, 教授 (10468639) 中嶋英治東京医科大学, 医学部, 講師 (60366143) 宮崎照雄東京医科大学, 医学部, 准教授 (60532687)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	27-ヒドロキシコレステロール / エストロゲン受容体 / 肺がん
Outline of Final Research Achievements	27-hydroxycholesterol (27HC) is synthesized from cholesterol mostly in alveolar macrophage, and promotes the proliferation of breast cancer cells as selective estrogen receptor modulator (SERM). We hypothesized that 27HC modulates ER-positive lung cancer growth. Cell growth of an ERβ-positive lung cell line (H23) was significantly promoted by adding more than 100 nM of 27HC. Besides, the addition of PHTPP, an antagonist of ERβ, canceled the growth promotion due to 27HC. In the tumor region collected from 13 lung cancer patients, 27HC content and the mRNA expressions of ERβ and its target gene c-Myc were significantly higher than in the non-tumor counterpart collected from same patient. These results suggest that 27HC can stimulate the growth of ER-positive lung cancer in vivo. Therefore, the inhibitions of 27HC production and ER activity may be new strategies to suppress the postoperative recurrence of ER-positive lung cancer in both genders.
Free Research Field	呼吸器外科
Academic Significance and Societal Importance of the Research Achievements	肺がんは発生率と死亡率共に，世界的に高く，2018年には210万人が罹患し、180万人が死亡している。本研究における成果は，エストロゲン受容体βの発現が確認された肺がんに対して，27-ヒドロキシコレステロールを合成する肺胞マクロファージの活性化をコントロールする事やエストロゲン受容体βの選択的阻害剤を用いる事で，術後の再発を抑制できる可能性が示唆された。新たな治療方法の開発や、27-ヒドロキシコレステロールが多く存在する他臓器がんでの検討など、応用範囲が広い研究成果と考えられる。