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Fibrotic enzymes modulate wound‐induced skin tumorigenesis
Author(s) -
Van Hove Lisette,
Lecomte Kim,
Roels Jana,
Vandamme Niels,
Vikkula HannaKaisa,
Hoorens Isabelle,
Ongenae Katia,
Hochepied Tino,
Donati Giacomo,
Saeys Yvan,
Quist Sven R,
Watt Fiona M,
van Loo Geert,
Hoste Esther
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202051573
Subject(s) - extracellular matrix , carcinogenesis , wound healing , biology , cancer associated fibroblasts , cancer research , microbiology and biotechnology , stroma , tumor microenvironment , pathology , fibroblast , matrix metalloproteinase , metastasis , context (archaeology) , cancer , immunology , cell culture , medicine , immunohistochemistry , genetics , paleontology , tumor cells
Fibroblasts are a major component of the microenvironment of most solid tumours. Recent research elucidated a large heterogeneity and plasticity of activated fibroblasts, indicating that their role in cancer initiation, growth and metastasis is complex and context‐dependent. Here, we performed genome‐wide expression analysis comparing fibroblasts in normal, inflammatory and tumour‐associated skin. Cancer‐associated fibroblasts (CAFs) exhibit a fibrotic gene signature in wound‐induced tumours, demonstrating persistent extracellular matrix (ECM) remodelling within these tumours. A top upregulated gene in mouse CAFs encodes for PRSS35, a protease capable of collagen remodelling. In human skin, we observed PRSS35 expression uniquely in the stroma of high‐grade squamous cell carcinomas. Ablation of PRSS35 in mouse models of wound‐ or chemically‐induced tumorigenesis resulted in aberrant collagen composition in the ECM and increased tumour incidence. Our results indicate that fibrotic enzymes expressed by CAFs can regulate squamous tumour initiation by remodelling the ECM.