title: Fibroblast activation and senescence in oral cancer.
abstract: There is now compelling evidence that the tumour stroma plays an important role in the pathogenesis of cancers of epithelial origin. The pre-eminent cell type of the stroma is carcinoma-associated fibroblasts. These cells demonstrate remarkable heterogeneity with activation and senescence being common stress responses. In this review, we summarise the part that these cells play in cancer, particularly oral cancer, and present evidence to show that activation and senescence reflect a unified programme of fibroblast differentiation. We report advances concerning the senescent fibroblast metabolome, mechanisms of gene regulation in these cells and ways in which epithelial cell adhesion is dysregulated by the fibroblast secretome. We suggest that the identification of fibroblast stress responses may be a valuable diagnostic tool in the determination of tumour behaviour and patient outcome. Further, the fact that stromal fibroblasts are a genetically stable diploid cell population suggests that they may be ideal therapeutic targets and early work in this context is encouraging.
authors.affiliation: Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: Prime
authors.affiliation: Melbourne Dental School and Oral Health CRC, University of Melbourne, Carlton, VIC, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Cirillo
authors.affiliation: Department of Dentistry, University of Jordan, Amman, Jordan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hassona
authors.affiliation: Integrated Biosciences, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Lambert
authors.affiliation: Department of Oral Biology and Biomedical Sciences and Oral Cancer Research and Co-ordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: I C
authors.initials: IC
authors.lastname: Paterson
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mellone
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Thomas
authors.affiliation: Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: E N L
authors.initials: EN
authors.lastname: James
authors.affiliation: Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: E K
authors.initials: EK
authors.lastname: Parkinson
mesh_terms: D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D055442:Metabolome; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
keywords: activation; cancer; fibroblasts; oral; senescence