Artículo
TGF‐β1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells
Picech, Florencia
; Sosa, Liliana del Valle
; Pérez, Pablo Aníbal
; Cecenarro, Laura Anahi; Oms, Sergio Rafael
; Coca, Hugo; de Battista, Juan Carlos
; Gutiérrez, Silvina
; Mukdsi, Jorge Humberto; Torres, Alicia Ines
; Petiti, Juan Pablo
Fecha de publicación:
10/2021
Editorial:
Wiley-liss, div John Wiley & Sons Inc.
Revista:
Journal of Cellular Physiology
ISSN:
0021-9541
e-ISSN:
1097-4652
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF-β1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF-β1 in WT and SSTR2-overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFβR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF-β1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH- and PRL-secretion and proliferation were improved in the presence of TGF-β1, as well as by SSTR2 overexpression. The OCT/TGF-β1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF-β1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF-β1/TGFβR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.
Palabras clave:
CELL PROLIFERATION
,
HORMONE SECRETION
,
OCTREOTIDE
,
SSTR2
,
TGF-Β1
,
TGFΒR
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CIDIE)
Articulos de CENTRO DE INV. Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Articulos de CENTRO DE INV. Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Articulos(INICSA)
Articulos de INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Articulos de INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Citación
Picech, Florencia; Sosa, Liliana del Valle; Pérez, Pablo Aníbal; Cecenarro, Laura Anahi; Oms, Sergio Rafael; et al.; TGF‐β1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Physiology; 236; 10; 10-2021; 6974-6987
Compartir
Altmétricas