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
© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:150 |
|---|---|
| Enthalten in: |
International journal of cancer - 150(2022), 11 vom: 01. Juni, Seite 1889-1904 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Maille, Elodie [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Amphiregulin |
|---|
| Anmerkungen: |
Date Completed 05.04.2022 Date Revised 15.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/ijc.33997 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM337930961 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM337930961 | ||
| 003 | DE-627 | ||
| 005 | 20231225235531.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ijc.33997 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1126.xml |
| 035 | |a (DE-627)NLM337930961 | ||
| 035 | |a (NLM)35262190 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Maille, Elodie |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a 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 |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.04.2022 | ||
| 500 | |a Date Revised 15.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a YAP | |
| 650 | 4 | |a amphiregulin | |
| 650 | 4 | |a malignant pleural mesothelioma | |
| 650 | 7 | |a Amphiregulin |2 NLM | |
| 700 | 1 | |a Levallet, Jérôme |e verfasserin |4 aut | |
| 700 | 1 | |a Dubois, Fatéméh |e verfasserin |4 aut | |
| 700 | 1 | |a Antoine, Martine |e verfasserin |4 aut | |
| 700 | 1 | |a Danel, Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Creveuil, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Mazieres, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Margery, Jacques |e verfasserin |4 aut | |
| 700 | 1 | |a Greillier, Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Gounant, Valérie |e verfasserin |4 aut | |
| 700 | 1 | |a Moro-Sibilot, Denis |e verfasserin |4 aut | |
| 700 | 1 | |a Molinier, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Léna, Hervé |e verfasserin |4 aut | |
| 700 | 1 | |a Monnet, Isabelle |e verfasserin |4 aut | |
| 700 | 1 | |a Bergot, Emmanuel |e verfasserin |4 aut | |
| 700 | 1 | |a Langlais, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Morin, Franck |e verfasserin |4 aut | |
| 700 | 1 | |a Scherpereel, Arnaud |e verfasserin |4 aut | |
| 700 | 1 | |a Zalcman, Gérard |e verfasserin |4 aut | |
| 700 | 1 | |a Levallet, Guénaëlle |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of cancer |d 1966 |g 150(2022), 11 vom: 01. Juni, Seite 1889-1904 |w (DE-627)NLM000004383 |x 1097-0215 |7 nnns |
| 773 | 1 | 8 | |g volume:150 |g year:2022 |g number:11 |g day:01 |g month:06 |g pages:1889-1904 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/ijc.33997 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 150 |j 2022 |e 11 |b 01 |c 06 |h 1889-1904 | ||