Ultraviolet light-induced collagen degradation inhibits melanoma invasion
Porter, Andrew; orcid: 0000-0002-3353-7002
Earnshaw, Charles H.; orcid: 0000-0002-7926-8506
Craig, Sarah; orcid: 0000-0003-1928-582X
Krutmann, Jean; orcid: 0000-0001-8433-1517
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.firstname.lastname@example.org
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AbstractAbstract: 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.
CitationNature Communications, volume 12, issue 1, page 2742
PublisherNature Publishing Group UK
DescriptionFrom 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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