hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/β1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.

Prognostic role of hERG1 Potassium Channels in Neuroendocrine Tumours of the Ileum and Pancreas / Iorio, Jessica; Antonuzzo, Lorenzo; Scarpi, Emanuela; D'Amico, Massimo; Duranti, Claudia; Messerini, Luca; Sparano, Clotilde; Caputo, Damiano; Lavacchi, Daniele; Borzomati, Domenico; Antonelli, Alice; Nibid, Lorenzo; Perrone, Giuseppe; Coppola, Alessandro; Coppola, Roberto; di Costanzo, Francesco; Lastraioli, Elena; Arcangeli, Annarosa. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 2022:(2022), pp. 1-18. [10.3390/ijms231810623]

Prognostic role of hERG1 Potassium Channels in Neuroendocrine Tumours of the Ileum and Pancreas

Iorio, Jessica;Antonuzzo, Lorenzo;Duranti, Claudia;Messerini, Luca;Sparano, Clotilde;Lavacchi, Daniele;di Costanzo, Francesco;Lastraioli, Elena
;
Arcangeli, Annarosa
2022

Abstract

hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/β1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.
2022
1
18
Goal 3: Good health and well-being
Iorio, Jessica; Antonuzzo, Lorenzo; Scarpi, Emanuela; D'Amico, Massimo; Duranti, Claudia; Messerini, Luca; Sparano, Clotilde; Caputo, Damiano; Lavacchi, Daniele; Borzomati, Domenico; Antonelli, Alice; Nibid, Lorenzo; Perrone, Giuseppe; Coppola, Alessandro; Coppola, Roberto; di Costanzo, Francesco; Lastraioli, Elena; Arcangeli, Annarosa
File in questo prodotto:
File Dimensione Formato  
ijms-23-10623-NET Iorio 2022.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Creative commons
Dimensione 2.24 MB
Formato Adobe PDF
2.24 MB Adobe PDF Visualizza/Apri

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1282218
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? ND
social impact