A novel pathomechanism of carcinogenesis caused by immune dysregulation to extracellular matrix molecules in lichen sclerosis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17313
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of Fukui
• Principal Investigator: Utsunomiya Natsuko 福井大学, 学術研究院医学系部門(附属病院部), 医員 (50792090)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 硬化性苔癬 / 細胞外基質 / ECM1 / laminin 332 / collagen 4 / collagen 7 / 皮膚線維芽細胞

Outline of Final Research Achievements

In the lesional skin of lichen sclerosus, the expression of major adhesion molecules, such as type IV/VII collagens and laminin 332 in the basement membrane was irregularly notched or thickened, and that of type IV collagen in the dermal vessel wall was swollen or duplicated. As anti-extracellular matrix protein 1 (ECM1) antibodies are present in the serum from a majority of patients, their antibody titer has been shown to correlate with disease severity and local tumorigenesis. Normal human fibroblasts with siRNA knockdown specific for ECM1 were analyzed by cDNA microarray. The expression levels of epithelial-mesenchymal transition-related molecules, as well as some basement membrane antigens, were altered.

Free Research Field

自己免疫性皮膚疾患

Academic Significance and Societal Importance of the Research Achievements

国内外の共同研究では、硬化性苔癬血清中の抗ECM1抗体を用いた癌化評価の医学的ニーズは高い。得られた研究成果が癌間質分子を標的とする創薬に結び付けば、癌自体を標的とする既存の抗癌剤との併用も可能な機序であり、相乗効果や耐性の獲得を一層回避できる治療戦略を構築できる。ECM1は固形癌や転移巣で過剰発現したり、ECM1機能異常がTh2タイプの気道過敏性を減弱させるなど、アレルギーや発癌などの多様性を担う。液性免疫異常を基盤に発症すると考えられる硬化性苔癬を基盤にして、①ECM1が皮膚老化や発癌イベントの上流に位置する分子、②他の疾患にもトレースし得るバイオマーカーの可能性を支持する結果につながる。