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    Ultraviolet light-induced collagen degradation inhibits melanoma invasion

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    Authors
    Budden, Timothy
    Gaudy-Marqueste, Caroline
    Porter, Andrew; orcid: 0000-0002-3353-7002
    Kay, Emily
    Gurung, Shilpa
    Earnshaw, Charles H.; orcid: 0000-0002-7926-8506
    Roeck, Katharina
    Craig, Sarah; orcid: 0000-0003-1928-582X
    Traves, Víctor
    Krutmann, Jean; orcid: 0000-0001-8433-1517
    Muller, Patricia
    Motta, Luisa
    Zanivan, Sara; orcid: 0000-0002-9880-9099
    Malliri, Angeliki; orcid: 0000-0001-6848-090X
    Furney, Simon J.; orcid: 0000-0002-8920-6800
    Nagore, Eduardo; orcid: 0000-0003-3433-8707
    Virós, Amaya; orcid: 0000-0001-5177-5015; email: Amaya.viros@cruk.manchester.ac.uk
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    Publication Date
    2021-05-12
    Submitted date
    2020-08-31
    
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    Abstract
    Abstract: Ultraviolet radiation (UVR) damages the dermis and fibroblasts; and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.
    Citation
    Nature Communications, volume 12, issue 1, page 2742
    Publisher
    Nature Publishing Group UK
    URI
    http://hdl.handle.net/10034/624547
    Type
    article
    Description
    From Springer Nature via Jisc Publications Router
    History: received 2020-08-31, accepted 2021-04-08, registration 2021-04-11, online 2021-05-12, pub-electronic 2021-05-12, collection 2021-12
    Publication status: Published
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