Ultraviolet light-induced collagen degradation inhibits melanoma invasion

Timothy Budden, Caroline Gaudy-Marqueste, Andrew Porter, Emily Kay, Shilpa Gurung, Charles H. Earnshaw, Katharina Roeck, Sarah Craig, Víctor Traves, Jean Krutmann, Patricia Muller, Luisa Motta, Sara Zanivan, Angeliki Malliri, Simon J. Furney, Eduardo Nagore and Amaya Virós ()
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Timothy Budden: The University of Manchester
Caroline Gaudy-Marqueste: Aix-Marseille University
Andrew Porter: The University of Manchester, Alderley Park
Emily Kay: University of Glasgow
Shilpa Gurung: The University of Manchester
Charles H. Earnshaw: The University of Manchester
Katharina Roeck: The University of Manchester
Sarah Craig: The University of Manchester
Víctor Traves: Institut Valencià Oncologia
Jean Krutmann: IUF – Leibniz Research Institute of Environmental Medicine
Patricia Muller: The University of Manchester
Luisa Motta: The University of Manchester
Sara Zanivan: University of Glasgow
Angeliki Malliri: The University of Manchester, Alderley Park
Simon J. Furney: Royal College of Surgeons in
Eduardo Nagore: Institut Valencià Oncologia
Amaya Virós: The University of Manchester

Nature Communications, 2021, vol. 12, issue 1, 1-13

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.

Date: 2021
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DOI: 10.1038/s41467-021-22953-z

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