A defect of amphiregulin release predicted ...
Document type :
Article dans une revue scientifique: Article original
DOI :
PMID :
Title :
A defect of amphiregulin release predicted longer survival independently of YAP expression in patients with pleural mesothelioma in the IFCT ‐0701 MAPS phase 3 trial
Author(s) :
Maille, Elodie [Auteur]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Levallet, Jérôme [Auteur]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Dubois, Fatéméh [Auteur]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Département de Pathologie [CHU Caen]
Antoine, Martine [Auteur]
CHU Tenon [AP-HP]
Danel, Claire [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Creveuil, Christian [Auteur]
CHU Caen
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Mazieres, Julien [Auteur]
Service Pneumologie et allergologie pédiatrique [CHU Toulouse]
Centre Hospitalier Universitaire de Toulouse [CHU Toulouse]
Margery, Jacques [Auteur]
Département de médecine oncologique [Gustave Roussy]
Institut Gustave Roussy [IGR]
Greillier, Laurent [Auteur]
Aix Marseille Université [AMU]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
Gounant, Valérie [Auteur]
CHU Tenon [AP-HP]
Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique [CIC 1425]
Moro‐sibilot, Denis [Auteur]
Pôle Thorax et Vaisseaux [CHU Grenoble]
Molinier, Olivier [Auteur]
Centre Hospitalier Le Mans (CH Le Mans)
Léna, Hervé [Auteur]
Service de pneumologie [Rennes] = Pneumology [Rennes]
Monnet, Isabelle [Auteur]
Centre Hospitalier Le Mans (CH Le Mans)
Bergot, Emmanuel [Auteur]
CHU Caen
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Langlais, Alexandra [Auteur]
Intergroupe Francophone de Cancérologie Thoracique [Paris] [IFCT]
Morin, Franck [Auteur]
Intergroupe Francophone de Cancérologie Thoracique [Paris] [IFCT]
Sherpereel, Arnaud [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Zalcman, Gérard [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique [CIC 1425]
Unité de génétique et biologie des cancers [U830]
Levallet, Guénaëlle [Auteur]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Département de Pathologie [CHU Caen]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Levallet, Jérôme [Auteur]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Dubois, Fatéméh [Auteur]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Département de Pathologie [CHU Caen]
Antoine, Martine [Auteur]
CHU Tenon [AP-HP]
Danel, Claire [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Creveuil, Christian [Auteur]
CHU Caen
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Mazieres, Julien [Auteur]
Service Pneumologie et allergologie pédiatrique [CHU Toulouse]
Centre Hospitalier Universitaire de Toulouse [CHU Toulouse]
Margery, Jacques [Auteur]
Département de médecine oncologique [Gustave Roussy]
Institut Gustave Roussy [IGR]
Greillier, Laurent [Auteur]
Aix Marseille Université [AMU]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
Gounant, Valérie [Auteur]
CHU Tenon [AP-HP]
Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique [CIC 1425]
Moro‐sibilot, Denis [Auteur]
Pôle Thorax et Vaisseaux [CHU Grenoble]
Molinier, Olivier [Auteur]
Centre Hospitalier Le Mans (CH Le Mans)
Léna, Hervé [Auteur]
Service de pneumologie [Rennes] = Pneumology [Rennes]
Monnet, Isabelle [Auteur]
Centre Hospitalier Le Mans (CH Le Mans)
Bergot, Emmanuel [Auteur]
CHU Caen
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Langlais, Alexandra [Auteur]
Intergroupe Francophone de Cancérologie Thoracique [Paris] [IFCT]
Morin, Franck [Auteur]
Intergroupe Francophone de Cancérologie Thoracique [Paris] [IFCT]
Sherpereel, Arnaud [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Zalcman, Gérard [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique [CIC 1425]
Unité de génétique et biologie des cancers [U830]
Levallet, Guénaëlle [Auteur]
GIP Cyceron [Cyceron]
Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales [ISTCT]
Département de Pathologie [CHU Caen]
Journal title :
International Journal of Cancer
Pages :
1889-1904
Publisher :
Wiley
Publication date :
2022-03-16
ISSN :
0020-7136
English keyword(s) :
amphiregulin
malignant pleural mesothelioma
YAP
malignant pleural mesothelioma
YAP
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
The Hippo pathway effector YAP is dysregulated in malignant pleural mesothelioma (MPM). YAP’s target genes include the secreted growth factor amphiregulin (AREG), which is overexpressed in a wide range of epithelial cancers ...
Show more >The Hippo pathway effector YAP is dysregulated in malignant pleural mesothelioma (MPM). YAP’s target genes include the secreted growth factor amphiregulin (AREG), which is overexpressed in a wide range of epithelial cancers and plays an elusive role in MPM. We assayed the expression of YAP and AREG in MPM pathology samples and that of AREG additionally in plasma samples of patients from the randomized phase 3 IFCT-0701 Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS) using immunohistochemistry and ELISA assays, respectively. MPM patients frequently presented high levels of tumor AREG (64.3%), a high cytosolic AREG expression being predictive of a better prognosis with longer median overall and progression-free survival. Surprisingly, tumor AREG cytosolic expression was not correlated with secreted plasma AREG. By investigating the AREG metabolism and function in MPM cell lines H2452, H2052, MSTO-211H, and H28, in comparison with the T47D ER+ breast cancer cell line used as a positive control, we confirm that AREG is important for cell invasion, growth without anchorage, proliferation, and apoptosis in mesothelioma cells. Yet, most of these MPM cell lines failed to correctly execute AREG post-translational processing by metalloprotease ADAM17/tumor necrosis factor-alpha-converting enzyme (TACE) and extra-cell secretion. The favorable prognostic value of high cytosolic AREG expression in MPM patients could therefore be sustained by default AREG post-translational processing and release. Thus, the determination of mesothelioma cell AREG content could be further investigated as a prognostic marker for MPM patients and used as a stratification factor in future clinical trials.Show less >
Show more >The Hippo pathway effector YAP is dysregulated in malignant pleural mesothelioma (MPM). YAP’s target genes include the secreted growth factor amphiregulin (AREG), which is overexpressed in a wide range of epithelial cancers and plays an elusive role in MPM. We assayed the expression of YAP and AREG in MPM pathology samples and that of AREG additionally in plasma samples of patients from the randomized phase 3 IFCT-0701 Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS) using immunohistochemistry and ELISA assays, respectively. MPM patients frequently presented high levels of tumor AREG (64.3%), a high cytosolic AREG expression being predictive of a better prognosis with longer median overall and progression-free survival. Surprisingly, tumor AREG cytosolic expression was not correlated with secreted plasma AREG. By investigating the AREG metabolism and function in MPM cell lines H2452, H2052, MSTO-211H, and H28, in comparison with the T47D ER+ breast cancer cell line used as a positive control, we confirm that AREG is important for cell invasion, growth without anchorage, proliferation, and apoptosis in mesothelioma cells. Yet, most of these MPM cell lines failed to correctly execute AREG post-translational processing by metalloprotease ADAM17/tumor necrosis factor-alpha-converting enzyme (TACE) and extra-cell secretion. The favorable prognostic value of high cytosolic AREG expression in MPM patients could therefore be sustained by default AREG post-translational processing and release. Thus, the determination of mesothelioma cell AREG content could be further investigated as a prognostic marker for MPM patients and used as a stratification factor in future clinical trials.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Comment :
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