Fiche publication
Date publication
juin 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr JUNG Alain
,
Mme LEDRAPPIER Sonia
,
Dr PENCREACH Erwan
,
Dr WASYLYK Bohdan
,
Dr COLIAT Pierre
Tous les auteurs :
Hanns E, Job S, Coliat P, Wasylyk C, Ramolu L, Pencreach E, Suarez-Carmona M, Herfs M, Ledrappier S, Macabre C, Abecassis J, Wasylyk B, Jung AC
Lien Pubmed
Résumé
OBJECTIVES: Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) patients have improved prognosis compared to other head and neck (HNSCC) cancers. Since poor prognosis is associated with tumour hypoxia, we studied whether the hypoxic response is different in HPV-related cells and tumours. MATERIAL AND METHODS: HPV-positive and -negative cells were incubated in hypoxia and analyzed by qRTPCR, western blotting and cell proliferation assays. Tumours formed by xenografting these cells in nude mice were studied by IHC. HNSCC patient samples were analyzed by unsupervised clustering of hypoxia-related gene expression, quantitative real-time PCR (qRTPCR) and immunohistochemical (IHC) detection of neo-blood vessels. RESULTS AND CONCLUSION: HPV-positive and -negative cells responded differently to hypoxia, in terms of gene expression (HIF-1alpha, PHD-3, GLUT-1 and VEGF-A) and cell survival. Tumour xenografts formed by HPV-positive cells had fewer hypoxic areas than those formed by HPV-negative cells. HPV related tumours were less hypoxic, expressed lower levels of hypoxia-responsive genes, and had a higher density of neo-blood vessels. HPV-related OSCC display lower tumour hypoxia, which could be linked to the distinct intrinsic abilities of HPV-positive tumour cells to adapt to hypoxia and to their better prognosis.
Référence
Oral Oncol. 2015 Jun 26. pii: S1368-8375(15)00237-7
