1. ¹Department of Experimental Pathology and Oncology, University of Firenze, Viale GB Morgagni, 50, 50134 Firenze, Italy
2. ²Department of Biotechnology and Biosciences, University of Milano Bicocca, Piazza della Scienza, 2, 20126 Milano, Italy
3. ³Department of Human Pathology and Oncology, University of Firenze, Viale GB Morgagni, 88, 50134 Firenze, Italy
4. ⁴Istituto Neurologico Besta, Via Celoria, 11, 20133 Milano, Italy
5. ⁵Department of Neurosurgery, University of Firenze, Largo P Palagi 1, 50139, Firenze, Italy

Correspondence: Dr A Arcangeli, E-mail: annarosa.arcangeli@unifi.it

⁶These authors contributed equally to this work

Revised 26 July 2005; Accepted 8 August 2005; Published online 20 September 2005.

Abstract

Recent studies have led to considerable advancement in our understanding of the molecular mechanisms that underlie the relentless cell growth and invasiveness of human gliomas. Partial understanding of these mechanisms has (1) improved the classification for gliomas, by identifying prognostic subgroups, and (2) pointed to novel potential therapeutic targets. Some classes of ion channels have turned out to be involved in the pathogenesis and malignancy of gliomas. We studied the expression and properties of K⁺ channels in primary cultures obtained from surgical specimens: human ether a gò-gò related (hERG)1 voltage-dependent K⁺ channels, which have been found to be overexpressed in various human cancers, and human ether a gò-gò-like 2 channels, that share many of hERG1's biophysical features. The expression pattern of these two channels was compared to that of the classical inward rectifying K⁺ channels, IRK, that are widely expressed in astrocytic cells and classically considered a marker of astrocytic differentiation. In our study, hERG1 was found to be specifically overexpressed in high-grade astrocytomas, that is, glioblastoma multiforme (GBM). In addition, we present evidence that, in GBM cell lines, hERG1 channel activity actively contributes to malignancy by promoting vascular endothelial growth factor secretion, thus stimulating the neoangiogenesis typical of high-grade gliomas. Our data provide important confirmation for studies proposing the hERG1 channel as a molecular marker of tumour progression and a possible target for novel anticancer therapies.