Ultraviolet light-induced collagen degradation inhibits melanoma invasion

Budden, T. et al. (2021) Ultraviolet light-induced collagen degradation inhibits melanoma invasion. Nature Communications, 12, 2742. (doi: 10.1038/s41467-021-22953-z) (PMID:33980846) (PMCID:PMC8115293)

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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.

Item Type:Articles
Additional Information:A.V. is a Wellcome Beit Fellow and personally funded by a Wellcome Trust Intermediate Fellowship (110078/Z/15/Z), and has work funded by Cancer Research UK (A27412) and Leo Pharma Foundation. E.N. is funded by Fondo de Investigación en Salud (FIS) PI15/01860, Instituto Carlos III, Spain. C.G.-M. funded by the French Dermatology Society, Collège des Enseignants en Dermatologie de France (CEDEF) and UNICANCER France. S.J.F. acknowledges support from the European Commission (FP7-PEOPLE-2013-IEF—6270270) and the Royal College of Surgeons in Ireland StAR programme. P.M. is funded by the Manchester Cancer Research Centre, supported by the CRUK Manchester Institute.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Zanivan, Professor Sara and Kay, Emily
Authors: Budden, T., Gaudy-Marqueste, C., Porter, A., Kay, E., Gurung, S., Earnshaw, C. H., Roeck, K., Craig, S., Traves, V., Krutmann, J., Muller, P., Motta, L., Zanivan, S., Malliri, A., Furney, S. J., Nagore, E., and Virós, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Nature Communications 12: 2742
Publisher Policy:Reproduced under a Creative Commons License

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