Titre
Stroma irradiation promotes CYR61/AV integrin-dependent tumour metastasts by suppressing angiogenesis
Type
abstract de conférence/colloque
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Série
Virchows Archiv
Auteur(s)
Monnier, Y.
Auteure/Auteur
Farmer, P.
Auteure/Auteur
Bieler, G.
Auteure/Auteur
Imaizumi, N.
Auteure/Auteur
Senstag, T.
Auteure/Auteur
Alghisi, G.C.
Auteure/Auteur
Stehle, J.C.
Auteure/Auteur
Andrejevic-Blant, S.
Auteure/Auteur
Moeckli, R.
Auteure/Auteur
Goodman, S.
Auteure/Auteur
Mirimanoff, R.O.
Auteure/Auteur
Delorenzi, M.
Auteure/Auteur
Ruegg, C.R.
Auteure/Auteur
Liens vers les unités
Titre du livre ou conférence/colloque
21th European Congress of Pathology
Adresse
Istanbul, Turkey, September 8-13, 2007
ISBN
0945-6317
Statut éditorial
Publié
Date de publication
2007
Volume
451
Première page
276
Peer-reviewed
Oui
Langue
anglais
Notes
Meeting Abstract
Résumé
Radiotherapy is successfully used to treat human cancers. However, patients locally recurring after treatment are at increased risk of developing metastases. The clinical management of this condition is a challenge, and its underlying mechanisms remain largely unknown. Since radiotherapy modifies the tumour microenvironment, we hypothesized that radiation-induced modifications of the tumour microenvironment might favour the spreading of metastatic tumour cells. Here, we report that the irradiation of naïve stroma promotes tumour metastasis through the suppression of angiogenesis, increased of tumour hypoxia and selection of aggressive tumour cell populations that retain an invasive and metastatic phenotype even when they leave their hypoxic microenvironment. Through gene expression profiling and gain and loss of function experiments, we identified the matricellular protein CYR61 as a critical mediator of tumour cell survival during hypoxia, invasion and metastasis. Inhibition of aV integrin prevented tumour cell invasion and metastasis induced by stroma irradiation and CYR61 over-expression. We found high CYR61 metagene expression to correlate with tumour hypoxia and shorter relapsefree survival in human breast cancer. These results identify CYR61 and aV-integrins as proteins that co-operate to mediate metastasis of tumours growing in irradiated stroma and as potential therapeutic targets in patients at risk for post-radiation recurrences. They also illustrate the potential impact of therapyinduced microenvironmental hypoxia in determining tumour evolution.
PID Serval
serval:BIB_126ACD7AFA19
Date de création
2008-04-28T09:35:42.310Z
Date de création dans IRIS
2025-05-20T19:04:22Z