Budden, TimothyGaudy-Marqueste, CarolinePorter, Andrew; orcid: 0000-0002-3353-7002Kay, EmilyGurung, ShilpaEarnshaw, Charles H; orcid: 0000-0002-7926-8506Roeck, KatharinaCraig, Sarah; orcid: 0000-0003-1928-582XTraves, VíctorKrutmann, Jean; orcid: 0000-0001-8433-1517Muller, PatriciaMotta, LuisaZanivan, Sara; orcid: 0000-0002-9880-9099Malliri, Angeliki; orcid: 0000-0001-6848-090XFurney, Simon J; orcid: 0000-0002-8920-6800Nagore, Eduardo; orcid: 0000-0003-3433-8707Virós, Amaya; orcid: 0000-0001-5177-5015; email: Amaya.viros@cruk.manchester.ac.uk2021-06-142021-06-142021-05-12Nature communications, volume 12, issue 1, page 2742http://hdl.handle.net/10034/624931From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-12Publication status: PublishedFunder: Wellcome Trust; Grant(s): 110078/Z/15/ZFunder: Cancer Research UK; Grant(s): A27412Ultraviolet 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.Licence for this article: cc byFibroblastsHumansLentivirusMelanomaCollagenCollagen Type IMicroscopy, Atomic ForceEnzyme-Linked Immunosorbent AssayUltraviolet RaysMass SpectrometryMatrix Metalloproteinase 1article2021-06-14