RT Journal Article
T1 LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors
A1 Sampedro Núñez, Miguel
A1 Bouthelier, Antonio
A1 Serrano Somavilla, Ana
A1 Martínez Hernández, Rebeca
A1 Adrados, Magdalena
A1 Martín Pérez, Elena
A1 Muñoz de Nova, José Luis
A1 Cameselle Teijeiro, José Manuel
A1 Blanco Carrera, Concepción
A1 Cabezas Agrícola, José Manuel
A1 Díaz, José Ángel
A1 García Centeno, Rogelio
A1 Aragonés, Julián
A1 Marazuela, Mónica
K1 Neuroendocrine tumors
K1 LAT-1
K1 GLUT-1
K1 Biomarker
K1 Gastroenteropancreatic neuroendocrine tumors
AB Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression (p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumors
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/23865
UL http://hdl.handle.net/10347/23865
LA eng
NO Sampedro-Núñez, M.; Bouthelier, A.; Serrano-Somavilla, A.; Martínez-Hernández, R.; Adrados, M.; Martín-Pérez, E.; Muñoz de Nova, J.L.; Cameselle-Teijeiro, J.M.; Blanco-Carrera, C.; Cabezas-Agricola, J.M.; Díaz, J.Á.; García-Centeno, R.; Aragones, J.; Marazuela, M. LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors. Cancers 2020, 12, 2968
NO This work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PIE13-0041, PI16-02091 and PI19-00584 (funded by Instituto de Salud Carlos III), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid), GETNE G1707 and GCI1901 (funded by Grupo Español de Tumores Neuroendocrinos y Endocrinos) and cofinanced by FEDER funds to M.M. Proyectos de Investigación en Salud (FIS) PI19/01316-FEDER (funded by Instituto de Salud Carlos III), given to J.C.T. Grants from the Ministerio de Economia y Competitividad (SAF2016-76815 and SAF2017-90794-REDT), and Fundació La Marato de TV3 (534/C/2016) ceded to J.A.
DS Minerva
RD 27 abr 2026