Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response

Acromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs. Our aim was to study...

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Autores: Gil, Joan, Marques-Pamies, Montserrat, Valassi, Elena, Garcia-Martinez, Araceli, Serra, Guillermo, Hostalot, Cristina, Fajardo-Montanana, Carmen, Carrato, Cristina, Bernabeu, Ignacio, Marazuela, Monica, Rodriguez-Lloveras, Helena, Camara, Rosa, Salinas, Isabel, Lamas, Cristina, Biagetti, Betina, Simo-Servat, Andreu, Webb, Susan M., Pico, Antonio, Jorda, Mireia, Puig-Domingo, Manel, REMAH Investigators
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/19644
Acceso en línea:https://hdl.handle.net/20.500.13003/19644
Access Level:acceso abierto
Palabra clave:epithelial-mesenchymal transition
acromegaly
somatostatin receptor ligands (SRLs)
somatostatin analogs (SSAs)
RORC
SNAI1
presurgical SRLs treatment
pituitary tumors
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spelling Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic ResponseGil, JoanMarques-Pamies, MontserratValassi, ElenaGarcia-Martinez, AraceliSerra, GuillermoHostalot, CristinaFajardo-Montanana, CarmenCarrato, CristinaBernabeu, IgnacioMarazuela, MonicaRodriguez-Lloveras, HelenaCamara, RosaSalinas, IsabelLamas, CristinaBiagetti, BetinaSimo-Servat, AndreuWebb, Susan M.Pico, AntonioJorda, MireiaPuig-Domingo, ManelREMAH Investigatorsepithelial-mesenchymal transitionacromegalysomatostatin receptor ligands (SRLs)somatostatin analogs (SSAs)RORCSNAI1presurgical SRLs treatmentpituitary tumorsAcromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs. Our aim was to study EMT and its relationship with SRLs resistance in GH-producing tumors. We analyzed the expression of EMT-related genes by RT-qPCR in 57 tumors. The postsurgical response to SRLs was categorized as complete response, partial response, or nonresponse if IGF-1 was normal, had decreased more than 30% without normalization, or neither of those, respectively. Most tumors showed a hybrid and variable EMT expression profile not specifically associated with SRL response instead of a defined epithelial or mesenchymal phenotype. However, high SNAll expression was related to invasive and SRL-nonresponsive tumors. RORC was overexpressed in tumors treated with SRLs before surgery, and this increased expression was more prominent in those cases that normalized postsurgical IGF-1 levels under SRL treatment. In conclusion, GH-producing tumors showed a heterogeneous expression pattern of EMT-related genes that would partly explain the heterogeneous response to SRLs. SNAI1 and RORC may be useful to predict response to SRLs and help medical treatment decision making.MDPI20222022-02-0120222022-02-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/19644reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/196442026-06-22T12:44:07Z
dc.title.none.fl_str_mv Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
title Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
spellingShingle Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
Gil, Joan
epithelial-mesenchymal transition
acromegaly
somatostatin receptor ligands (SRLs)
somatostatin analogs (SSAs)
RORC
SNAI1
presurgical SRLs treatment
pituitary tumors
title_short Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
title_full Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
title_fullStr Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
title_full_unstemmed Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
title_sort Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
dc.creator.none.fl_str_mv Gil, Joan
Marques-Pamies, Montserrat
Valassi, Elena
Garcia-Martinez, Araceli
Serra, Guillermo
Hostalot, Cristina
Fajardo-Montanana, Carmen
Carrato, Cristina
Bernabeu, Ignacio
Marazuela, Monica
Rodriguez-Lloveras, Helena
Camara, Rosa
Salinas, Isabel
Lamas, Cristina
Biagetti, Betina
Simo-Servat, Andreu
Webb, Susan M.
Pico, Antonio
Jorda, Mireia
Puig-Domingo, Manel
REMAH Investigators
author Gil, Joan
author_facet Gil, Joan
Marques-Pamies, Montserrat
Valassi, Elena
Garcia-Martinez, Araceli
Serra, Guillermo
Hostalot, Cristina
Fajardo-Montanana, Carmen
Carrato, Cristina
Bernabeu, Ignacio
Marazuela, Monica
Rodriguez-Lloveras, Helena
Camara, Rosa
Salinas, Isabel
Lamas, Cristina
Biagetti, Betina
Simo-Servat, Andreu
Webb, Susan M.
Pico, Antonio
Jorda, Mireia
Puig-Domingo, Manel
REMAH Investigators
author_role author
author2 Marques-Pamies, Montserrat
Valassi, Elena
Garcia-Martinez, Araceli
Serra, Guillermo
Hostalot, Cristina
Fajardo-Montanana, Carmen
Carrato, Cristina
Bernabeu, Ignacio
Marazuela, Monica
Rodriguez-Lloveras, Helena
Camara, Rosa
Salinas, Isabel
Lamas, Cristina
Biagetti, Betina
Simo-Servat, Andreu
Webb, Susan M.
Pico, Antonio
Jorda, Mireia
Puig-Domingo, Manel
REMAH Investigators
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv epithelial-mesenchymal transition
acromegaly
somatostatin receptor ligands (SRLs)
somatostatin analogs (SSAs)
RORC
SNAI1
presurgical SRLs treatment
pituitary tumors
topic epithelial-mesenchymal transition
acromegaly
somatostatin receptor ligands (SRLs)
somatostatin analogs (SSAs)
RORC
SNAI1
presurgical SRLs treatment
pituitary tumors
description Acromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs. Our aim was to study EMT and its relationship with SRLs resistance in GH-producing tumors. We analyzed the expression of EMT-related genes by RT-qPCR in 57 tumors. The postsurgical response to SRLs was categorized as complete response, partial response, or nonresponse if IGF-1 was normal, had decreased more than 30% without normalization, or neither of those, respectively. Most tumors showed a hybrid and variable EMT expression profile not specifically associated with SRL response instead of a defined epithelial or mesenchymal phenotype. However, high SNAll expression was related to invasive and SRL-nonresponsive tumors. RORC was overexpressed in tumors treated with SRLs before surgery, and this increased expression was more prominent in those cases that normalized postsurgical IGF-1 levels under SRL treatment. In conclusion, GH-producing tumors showed a heterogeneous expression pattern of EMT-related genes that would partly explain the heterogeneous response to SRLs. SNAI1 and RORC may be useful to predict response to SRLs and help medical treatment decision making.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-02-01
2022
2022-02-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/19644
url https://hdl.handle.net/20.500.13003/19644
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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