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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

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...

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Autores principales: Maille, Elodie, Levallet, Jérôme, Dubois, Fatéméh, Antoine, Martine, Danel, Claire, Creveuil, Christian, Mazieres, Julien, Margery, Jacques, Greillier, Laurent, Gounant, Valérie, Moro‐Sibilot, Denis, Molinier, Olivier, Léna, Hervé, Monnet, Isabelle, Bergot, Emmanuel, Langlais, Alexandra, Morin, Franck, Scherpereel, Arnaud, Zalcman, Gérard, Levallet, Guénaëlle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545369/
https://www.ncbi.nlm.nih.gov/pubmed/35262190
http://dx.doi.org/10.1002/ijc.33997
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author Maille, Elodie
Levallet, Jérôme
Dubois, Fatéméh
Antoine, Martine
Danel, Claire
Creveuil, Christian
Mazieres, Julien
Margery, Jacques
Greillier, Laurent
Gounant, Valérie
Moro‐Sibilot, Denis
Molinier, Olivier
Léna, Hervé
Monnet, Isabelle
Bergot, Emmanuel
Langlais, Alexandra
Morin, Franck
Scherpereel, Arnaud
Zalcman, Gérard
Levallet, Guénaëlle
author_facet Maille, Elodie
Levallet, Jérôme
Dubois, Fatéméh
Antoine, Martine
Danel, Claire
Creveuil, Christian
Mazieres, Julien
Margery, Jacques
Greillier, Laurent
Gounant, Valérie
Moro‐Sibilot, Denis
Molinier, Olivier
Léna, Hervé
Monnet, Isabelle
Bergot, Emmanuel
Langlais, Alexandra
Morin, Franck
Scherpereel, Arnaud
Zalcman, Gérard
Levallet, Guénaëlle
author_sort Maille, Elodie
collection PubMed
description 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 posttranslational processing by metalloprotease ADAM17/tumor necrosis factor‐alpha‐converting enzyme (TACE) and extracell secretion. The favorable prognostic value of high cytosolic AREG expression in MPM patients could therefore be sustained by default AREG posttranslational 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.
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spelling pubmed-95453692022-10-14 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 Maille, Elodie Levallet, Jérôme Dubois, Fatéméh Antoine, Martine Danel, Claire Creveuil, Christian Mazieres, Julien Margery, Jacques Greillier, Laurent Gounant, Valérie Moro‐Sibilot, Denis Molinier, Olivier Léna, Hervé Monnet, Isabelle Bergot, Emmanuel Langlais, Alexandra Morin, Franck Scherpereel, Arnaud Zalcman, Gérard Levallet, Guénaëlle Int J Cancer Molecular Cancer Biology 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 posttranslational processing by metalloprotease ADAM17/tumor necrosis factor‐alpha‐converting enzyme (TACE) and extracell secretion. The favorable prognostic value of high cytosolic AREG expression in MPM patients could therefore be sustained by default AREG posttranslational 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. John Wiley & Sons, Inc. 2022-03-16 2022-06-01 /pmc/articles/PMC9545369/ /pubmed/35262190 http://dx.doi.org/10.1002/ijc.33997 Text en © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Molecular Cancer Biology
Maille, Elodie
Levallet, Jérôme
Dubois, Fatéméh
Antoine, Martine
Danel, Claire
Creveuil, Christian
Mazieres, Julien
Margery, Jacques
Greillier, Laurent
Gounant, Valérie
Moro‐Sibilot, Denis
Molinier, Olivier
Léna, Hervé
Monnet, Isabelle
Bergot, Emmanuel
Langlais, Alexandra
Morin, Franck
Scherpereel, Arnaud
Zalcman, Gérard
Levallet, Guénaëlle
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort defect of amphiregulin release predicted longer survival independently of yap expression in patients with pleural mesothelioma in the ifct‐0701 maps phase 3 trial
topic Molecular Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545369/
https://www.ncbi.nlm.nih.gov/pubmed/35262190
http://dx.doi.org/10.1002/ijc.33997
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