Identification of melanocyte stem cells in acral palmoplantar skin and elucidation of the early developmental mechanism of acral melanoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H00532
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: The University of Tokyo (2022); Tokyo Medical and Dental University (2020-2021)
• Principal Investigator: Nishimura Emi 東京大学, 医科学研究所, 教授 (70396331)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: メラノーマ / 癌 / 幹細胞 / 診断 / オリジン / 悪性 / 汗腺 / 皮膚

Outline of Final Research Achievements

Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences
are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly
cancers that occur on non-hair-bearing skin, have distinct origins, we developed fate-tracing technologies of melanocyte stem cells ( McSC) in sweat glands and in melanomamodels in mice and compare the cellular dynamics with human melanoma. The results revealed that those McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin demonstrated that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.

Free Research Field

実験病理

Academic Significance and Societal Importance of the Research Achievements

本研究は世界ではじめて汗腺内の色素幹細胞の遺伝学的系譜解析に成功し、末端部型悪性黒色腫のオリジンの同定に成功した。同時に、ヒトの末端部型悪性黒色腫を模倣するマウスモデルの作製に成功し、末端部型悪性黒色腫の治療薬の有効性評価や病理発生機序や病態の解明に役立つ実験系をはじめて提供できるようになった。さらに末端部の悪性黒色腫は予後の極めて悪い皮膚癌として知られ、母斑との鑑別診断が極めて重要であるが、比較的簡便な免疫組織学的な解析によりメラノーマ細胞の分布を確認することによって悪性と良性の鑑別診断がはじめて可能となった。特に早期の鑑別診断は熟練した皮膚病理医にとっても困難なことが多いため意義は大きい。