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, 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
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 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.

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