Usefulness of vitamin D administration based on elucidation of the mechanism of cancerous skeletal muscle atrophy

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K19405
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: Miyagawa Yoshihiro 国立研究開発法人国立長寿医療研究センター, ジェロサイエンス研究センター, 研究員 (70867291)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: がん悪液質 / 骨格筋 / ビタミンD / 骨格筋萎縮 / がんリハビリテーション

Outline of Final Research Achievements

Cancer cachexia frequently develops in patients with advanced-stage cancer and is an important prognostic factor, but no specific treatment has been developed to date. In this study, we first generated an in vitro model of cancer cachexia, which showed atrophy of myotubular cells and increased Vdr expression. Next, we generated a cancer cachexia model using skeletal muscle-specific Vdr-deficient mice, and found that knockout of Vdr in skeletal muscle in cancer cachexia resulted in a decrease in muscle weight and a reduction in myofiber cross-sectional area. Furthermore, knockout of Vdr markedly increased the expression of muscle atrophy-related factors in the tibialis anterior muscle. These results suggest that the increased expression of Vdr in skeletal muscle in cancer cachexia may be a protective response to resist muscle atrophy.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、がん悪液質でのVDRの役割について骨格筋特異的VDR欠損マウスとがん悪液質モデルを組み合わせた初めての報告であり、VDRの発現増加が筋萎縮に抵抗するための反応である可能性を示す重要な知見である。今後、他のがん細胞を用いた悪液質モデルにおいても同様の反応を示すか検証していく必要があるが、本研究結果はがん悪液質による骨格筋萎縮に対し、VDRを標的とした治療法の開発に貢献することが期待される。