2021 Fiscal Year Final Research Report
Genome-wide screening of the key molecules for metastasizing collagen VII-deficient squamous cell carcinoma.
| Project/Area Number |
19K08764
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西江 渉 北海道大学, 医学研究院, 客員教授 (20443955)
柳 輝希 北海道大学, 大学病院, 講師 (50755973)
泉 健太郎 北海道大学, 医学研究院, 助教 (50793668)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | VII型コラーゲン / 有棘細胞癌 / 遠隔転移 / 網羅的ゲノムスクリーニング / CRISPR/Cas9 |
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| Outline of Final Research Achievements |
The aim of this study was to elucidate the metastatic mechanism of squamous cell carcinoma (SCC) arising in patients with dystrophic epidermolysis bullosa (DEB) caused by mutations in type 7 collagen (COL7) gene. DEB patient model keratinocytes with a comprehensive gene-editing did not develop metastasis when transplanted subcutaneously in mice, but the subcutaneous tumors of DEB patient model showed an overall irregular structure, surrounding fibrosis, and hypervascularization compared to subcutaneous tumors of normal keratinocytes. These results suggest that subcutaneous tumors in DEB patient model induce changes in the surrounding tissue environment via abnormal construction of the basement membrane, and that these changes may contribute to the metastatic mechanism of SCC in DEB patients.
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| Free Research Field |
皮膚科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、栄養障害型表皮水疱症患者（DEB）の表皮細胞は癌化する前に血管増生などの遠隔転移に繋がる組織環境を作ることが明らかとなった。今までは、線維芽細胞が主に関連するTGF-βの持続的な活性化に伴う慢性炎症がDEB患者の表皮細胞を取り囲む組織環境を変化させていると考えられてきた。本研究で得られた、DEB患者の表皮細胞自体が周囲の組織環境を遠隔転移しやすいように変化させる新たな知見は、今後DEB患者の表皮細胞を標的とした有棘細胞癌の予防法や治療法の可能性を示唆する。
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