hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma

作者：Lastraioli E; Perrone G; Sette A; Fiore A; Crociani O; Manoli S; D'Amico M; Masselli M; Iorio J; Callea M; Borzomati D; Nappo G; Bartolozzi F; Santini D; Bencini L; Farsi M; Boni L; Di Costanzo F; Schwab A; Muda A Onetti; Coppola R; Arcangeli A^*

来源：British Journal of Cancer, 2015, 112(6): 1076-1087.

DOI：10.1038/bjc.2015.28

• pancreatic ductal adenocarcinoma (PDAC)
• hERG1 potassium channels
• EGF-R
• prognosis
• molecular-imaging

Background: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking.
Methods: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (alpha-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre, LSL-Kras(G12D/+), LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled alpha-hERG1-MoAb.
Results: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the alpha-hERG1-MoAb could detect PDAC in vivo.
Conclusions: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

• 出版日期2015-3-17