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    Ultraviolet light-induced collagen degradation inhibits melanoma invasion

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    Authors
    Budden, Timothy
    Gaudy-Marqueste, C.
    Porter, Andrew P
    Kay, E.
    Gurung, Shilpa
    Earnshaw, Charles
    Roeck, K.
    Craig, S.
    Traves, V.
    Krutmann, J.
    Muller, Patricia
    Motta, L.
    Zanivan, S.
    Malliri, A.
    Furney, S. J.
    Nagore, E
    Virós, Amaya
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    Affiliation
    Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK
    Issue Date
    2021
    
    Metadata
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    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
    Budden T, Gaudy-Marqueste C, Porter A, Kay E, Gurung S, Earnshaw CH, et al. Ultraviolet light-induced collagen degradation inhibits melanoma invasion. Nat Commun. 2021 May 12;12(1).
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/624125
    DOI
    10.1038/s41467-021-22953-z
    PubMed ID
    33980846
    Additional Links
    https://dx.doi.org/10.1038/s41467-021-22953-z
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-021-22953-z
    Scopus Count
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    All Paterson Institute for Cancer Research

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