Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
Gil, Joan (Institut d'Investigació Biomèdica Sant Pau)
Marques-Pamies, Montserrat (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Valassi, Elena (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
García-Martínez, Araceli (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Serra, Guillermo (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Hostalot, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Fajardo-Montañana, Carmen (Hospital Universitari de la Ribera (València))
Carrato, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Bernabeu Morón, Ignacio (Hospital Clínico Universitario (Santiago de Compostela, Galícia))
Marazuela, Mónica (Hospital Universitario de la Princesa (Madrid))
Rodríguez-Lloveras, Helena (Institut Germans Trias i Pujol)
Cámara, Rosa (Hospital Universitari i Politècnic La Fe (València))
Salinas, Isabel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Lamas, Cristina (Complejo Hospitalario Universitario de Albacete)
Biagetti, Betina (Hospital Universitari Vall d'Hebron)
Simó-Servat, Andreu (Mútua de Terrassa)
Webb, S. M 1952- (Institut d'Investigació Biomèdica Sant Pau)
Picó Alfonso, Antonio M (Universidad de Miguel Hernández de Elche)
Jordà, Mireia (Institut Germans Trias i Pujol)
Puig Domingo, Manuel (Universitat Autònoma de Barcelona. Departament de Medicina)
Date: |
2022 |
Abstract: |
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 SNAI1 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. |
Grants: |
Instituto de Salud Carlos III PMP 15/00027
|
Rights: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Language: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Subject: |
Epithelial-mesenchymal transition ;
Acromegaly ;
Somatostatin receptor ligands (SRLs) ;
Somatostatin analogs (SSAs) ;
RORC ;
SNAI1 ;
Presurgical SRLs treatment ;
Pituitary tumors |
Published in: |
Biomedicines, Vol. 10 (february 2022) , ISSN 2227-9059 |
DOI: 10.3390/biomedicines10020460
PMID: 35203668
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Record created 2022-04-26, last modified 2024-05-22