Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa.

[dystrophic epidermolysis bullosa]

Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB ) develop aggressive cutaneous squamous cell carcinoma (cSCC ). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC . Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples . Although gene expression of RDEB normal skin fibroblasts resembled that of cancer -associated fibroblasts , RDEB cancer -associated fibroblasts exhibited a distinct and divergent gene expression profile , with a large proportion of the differentially expressed genes involved in matrix and cell adhesion . RDEB cancer -associated fibroblasts conferred increased adhesion and invasion to tumor and nontumor keratinocytes . Reduction of COL 7 A 1 , the defective gene in RDEB , in normal dermal fibroblasts led to increased type XII collagen , thrombospondin-1 , and Wnt-5 A , while reexpression of wild type COL 7 A 1 in RDEB fibroblasts decreased type XII collagen , thrombospondin-1 , and Wnt-5 A expression , reduced tumor cell invasion in organotypic culture , and restricted tumor growth in vivo . Overall , our findings show that matrix composition in patients with RDEB is a permissive environment for tumor development , and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer -associated fibroblasts .

Diseases
Validation

Diseases presenting "mortality is greater in rdeb than in other patient groups with cscc" symptom

dystrophic epidermolysis bullosa

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