| Title: | Ultraviolet light-induced collagen degradation inhibits melanoma invasion |
| Journal: | Nature Communications |
| Published: | 12 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33980846/ |
| DOI: | https://doi.org/10.1038/s41467-021-22953-z |
| URL: | https://durham-repository.worktribe.com/output/1225533 |
Publication 7628
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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.</p>
12 Keywords
- Collagen
- Collagen Type I
- Collagen Type I, alpha 1 Chain
- Enzyme-Linked Immunosorbent Assay
- Fibroblasts
- Humans
- Lentivirus
- Mass Spectrometry
- Matrix Metalloproteinase 1
- Melanoma
- Microscopy, Atomic Force
- Ultraviolet Rays
17 Authors
- 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
- Amaya Virós
Enabling scientific discoveries that improve human health