Human neoplastic mesothelial cells express voltage-gated sodium channels involved in cell motility.
Given the pivotal role of ion channels in neoplastic transformation, the aim of the present study has been to assess possible differences in the expression patterns of voltage-gated monovalent cationic (Na(+) and K(+)) currents between normal and neoplastic mesothelial cells (NM, MPM, respectively), and to evaluate the role of specific ion channels in mesothelioma cells proliferation, apoptosis, and motility. To achieve this aim, membrane currents expressed in NM and MPM cells derived from surgically-removed human specimens were investigated by means of patch-clamp electrophysiology. NM cells were found to express three main classes of K(+) currents, which were defined as K(IR), maxiK(Ca), and K(V) currents on the basis of their biophysical and pharmacological properties. Each of these K(+) currents was absent in MPM cells; by contrast, MPM cells revealed the novel appearance of tetrodotoxin (TTX)-sensitive voltage-gated Na(+) currents undetected in normal mesothelial cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR analysis of MPM cells transcripts showed significant expression of the mRNAs encoding for Na(V)1.2, and Na(V)1.6, and Na(V)1.7 (and less so for Na(V)1.3, Na(V)1.4, and Na(V)1.5) main voltage-gated sodium channel (VGSC) alpha-subunit(s). Interestingly, blockade of VGSCs with TTX decreased mesothelioma cell migration in in vitro motility assays; on the other hand, TTX failed to interfere with cell viability, proliferation, and apoptosis progression triggered by UV exposure. In summary, the results of the present study suggest that VGSCs expression in MPM cells may favor the increased motility of the neoplastic cells, a phenotypic feature often associated with the malignant phenotype.
Fulgenzi
Gianluca
G
Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Via Ranieri, Ancona 60131, Italy.
Graciotti
Laura
L
Faronato
Monica
M
Soldovieri
Maria Virginia
MV
Miceli
Francesco
F
Amoroso
Salvatore
S
Annunziato
Lucio
L
Procopio
Antonio
A
Taglialatela
Maurizio
M
D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D004594:Electrophysiology / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology*; D018301:Neoplasms, Mesothelial / Q000473:pathology / Q000503:physiopathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D015222:Sodium Channels / Q000032:analysis* / Q000378:metabolism
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels