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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Detalles Bibliográficos
Autores: Gil, Joan, Marques-Pamies, Montserrat, Valassi, Elena, García-Martínez, Araceli, Serra, Guillermo, Hostalot, Cristina, Fajardo-Montañana, Carmen, Carrato, Cristina, Bernabeu, Ignacio, Marazuela Azpiroz, Mónica, Rodríguez-Lloveras, Helena, Cámara, Rosa, Salinas, Isabel, Lamas, Cristina, Biagetti, Betina, Simó-Servat, Andreu, Webb, Susan M., Picó, Antonio, Jordà, Mireia, Puig-Domingo, Manel
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/706677
Acceso en línea:http://hdl.handle.net/10486/706677
https://dx.doi.org/10.3390/biomedicines10020460
Access Level:acceso abierto
Palabra clave:Acromegaly
Epithelial-mesenchymal transition
Pituitary tumors
Presurgical SRLs treatment
RORC
SNAI1
Somatostatin analogs (SSAs)
Somatostatin receptor ligands (SRLs)
Medicina
Descripción
Sumario: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

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