title: Stromal microenvironment in type VII collagen-deficient skin: The ground for squamous cell carcinoma development.
abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disease caused by mutations that affect the function and/or the amount of type VII collagen (C7), the major component of anchoring fibrils. Hallmarks of RDEB are unremitting blistering and chronic wounds leading to tissue fibrosis and scarring. Nearly all patients with severe RDEB develop highly metastatic squamous cell carcinomas (SCC) which are the main cause of death. Accumulating evidence from a murine RDEB model and human RDEB cells demonstrates that lack of C7 also directly alters the wound healing process. Non-healing RDEB wounds are characterized by increased inflammation, high transforming growth factor-β1 (TGF-β1) levels and activity, and are heavily populated by myofibroblasts responsible for enhanced fibrogenesis and matrix stiffness. These changes make the RDEB stroma a microenvironment prone to cancer initiation, where cells with features of cancer-associated fibroblasts are found. Here, we discuss recent knowledge on microenvironment alterations in RDEB, highlighting possible therapeutic targets to prevent and/or delay fibrosis and SCC development.
authors.affiliation: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Guerra
authors.affiliation: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Odorisio
authors.affiliation: Genetic and Rare Diseases Research Area and Dermatology Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.affiliation: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy. Electronic address: d.castiglia@idi.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D024143:Collagen Type VII / Q000235:genetics*; D018450:Disease Progression; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000473:pathology; D006801:Humans; D011230:Precancerous Conditions / Q000235:genetics*; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: C569053:COL7A1 protein, human; D024143:Collagen Type VII
keywords: Cutaneous basement membrane zone; Epithelial cancer; Extracellular matrix; Losartan; Proinflammatory cytokines; Repurposing drugs