Discovery - University of Dundee - Online Publications

Library & Learning Centre

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

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

Research output: Contribution to journalArticle

View graph of relations

Authors

  • Yi-Zhen Ng
  • Celine Pourreyron
  • Julio C. Salas-Alanis
  • Jasbani H. S. Dayal
  • Rodrigo Cepeda-Valdes
  • Wenfei Yan
  • Sheila Wright
  • Mei Chen
  • Jo-David Fine
  • Fiona J. Hogg
  • John A. McGrath
  • Dedee F. Murrell
  • Irene M. Leigh
  • E. Birgit Lane
  • Andrew P. South (Lead / Corresponding author)

Research units

Info

Original languageEnglish
Pages3522-3534
Number of pages13
JournalCancer Research
Journal publication date2012
Journal number14
Volume72
DOIs
StatePublished

Abstract

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 non-tumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1, and Wnt-5A, while reexpression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin-1, and Wnt-5A 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. ©2012 AACR.

Documents

Library & Learning Centre

Contact | Accessibility | Policy