Progression of genotype-specific oral cancer leads to senescence of cancer-associated fibroblasts and is mediated by oxidative stress and TGF-beta
Yazan Hassona, Nicola Cirillo, Kue Peng Lim, Andrew Herman, Max Mellone, Gareth J Thomas, Gayani N Pitiyage, E Ken Parkinson, Stephen S Prime
CARCINOGENESIS | OXFORD UNIV PRESS | Published : 2013
Keratinocyte senescence acts as a barrier to tumor progression but appears to be lost in late pre-malignancy to yield genetically unstable oral squamous cell carcinomas (GU-OSCC); a subset of OSCC possessing wild-type p53 and are genetically stable (GS-OSCC). In this study, fibroblasts from GU-OSCC were senescent relative to fibroblasts from GS-OSCC, epithelial dysplastic tissues or normal oral mucosa, as demonstrated by increased senescence-associated β-galactosidase (SA β-Gal) activity and overexpression of p16(INK4A). Keratinocytes from GU-OSCC produced high levels of reactive oxygen species (ROS) and this was associated with an increase in the production of transforming growth factor-β1 ..View full abstract
Y.H. is a recipient of a Clinical Fellowship from the University of Jordan.