1. Phase-specific signatures of wound fibroblasts and matrix patterns define cancer-associated fibroblast subtypes
- Author
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Mateusz S. Wietecha, David Lauenstein, Michael Cangkrama, Sybille Seiler, Juyoung Jin, Andreas Goppelt, Manfred Claassen, Mitchell P. Levesque, Reinhard Dummer, Sabine Werner, and University of Zurich
- Subjects
collagen ,Cancer ,cancer-associated fibroblast ,elastin ,wound healing ,10177 Dermatology Clinic ,610 Medicine & health ,Molecular Biology - Abstract
Healing wounds and cancers present remarkable cellular and molecular parallels, but the specific roles of the healing phases are largely unknown. We developed a bioinformatics pipeline to identify genes and pathways that define distinct phases across the time-course of healing. Their comparison to cancer transcriptomes revealed that a resolution phase wound signature is associated with increased severity in skin cancer and enriches for extracellular matrix-related pathways. Comparisons of transcriptomes of early- and late-phase wound fibroblasts vs skin cancer-associated fibroblasts (CAFs) identified an "early wound" CAF subtype, which localizes to the inner tumor stroma and expresses collagen-related genes that are controlled by the RUNX2 transcription factor. A "late wound" CAF subtype localizes to the outer tumor stroma and expresses elastin-related genes. Matrix imaging of primary melanoma tissue microarrays validated these matrix signatures and identified collagen- vs elastin-rich niches within the tumor microenvironment, whose spatial organization predicts survival and recurrence. These results identify wound-regulated genes and matrix patterns with prognostic potential in skin cancer., Matrix Biology, 119, ISSN:0945-053X, ISSN:1569-1802
- Published
- 2023