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LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors

Miguel Sampedro-Núñez, Antonio Bouthelier, Ana Serrano-Somavilla, Rebeca Martínez-Hernández, Magdalena Adrados, Elena Martín-Pérez, José Luis Muñoz de Nova, José Manuel Cameselle-Teijeiro, Concepción Blanco-Carrera, José Manuel Cabezas-Agricola, José Ángel Díaz, Rogelio García-Centeno (+2 others)
2020 Cancers  

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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
more » ... P-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.
doi:10.3390/cancers12102968 pmid:33066332 fatcat:gzeyjpgzd5am3mum5hp7fgugzm
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Miguel Sampedro-Núñez, Antonio Bouthelier, Ana Serrano-Somavilla, Rebeca Martínez-Hernández, Magdalena Adrados, Elena Martín-Pérez, José Luis Muñoz de Nova, José Manuel Cameselle-Teijeiro, Concepción Blanco-Carrera, José Manuel Cabezas-Agricola, José Ángel Díaz, Rogelio García-Centeno, Julian Aragones, Mónica Marazuela. "LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors." Cancers 12.10 (2020) 2968