Stereotactic Radiosurgery Effect on Ion Channel Activity: Implications in Metastasis and Cancer Pain Relief

Abstract

Influence of aberrantly expression ofvoltage‐gated sodium channels (VGSCs) in metabolic regulation, cell cycledistribution, proliferation, radioresistance and metastasis confirm their role incarcinogenesis. Recently VGSCs have been proposed as prognostic markers andantimetastatic targets with diagnostic and therapeutic potential [1]. Increasedsodium levels observed in cancer tissue, due to the persistent currents thatVGSCs develop under hypoxic conditions, have been correlated to tumor growth, invasiveness and metastasis [2]. Quality of life of bone metastasis patientssignificantly improves after radiotherapy (10 fractions of 3Gy or 1 fraction of8 Gy) due to the control of tumor spreading and the sustained pain relief [3, 4]. Mechanism trough which radiotherapy controls tumor spread and achieves painrelief is poorly understood. In the present work the role of VGSCs in tumorcontrol and pain relief mechanisms after irradiation were analyzed by invasionassays and whole‐cell patch clamp. Monolayers of NaV1.7 expressing and wildtype CHO cells were irradiated in a LINAC. SL 15 Phillips (8X8 cm2 field, 6MV xrays, gantry 180°) before evaluating the clonal and invasive capacity of cellsand the function of NaV1.7. Resuls show that NaV1.7 expression reduces CHOcells plating efficiency and confers radioresistance. Irradiation reduces sodiumcurrent density and increased the voltage to hyperpolarize. Apparently, irradiationdelayed NaV1.7 activation and significantly abolished invasiveness induced byradiotherapy. Support or Funding Information This study was performed as part of the activities of the “Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos‐CONACyT”. Grant 293334. NaV1.7 expression reduces CHO cells plating efficiency and confers radioresistance NaV1.7 expression (red line) confers radioresistance to CHO cells (black line) In Vivo Evidence for Voltage-GatedSodium Channel Expression in Carcinomas and Potentiation of MetastasisMBA.DjamgozSP.FraserWJ.BrackenburyCancers(Basel)1111E1675E1695Colorectal cancer invasiveness in vitro: Predominantcontribution of neonatal Nav1.5 under normoxia and hypoxiaRM.GuzelK.OgmenKMIlievaSP.FraserMBA.DjamgozJ. Cell. Physiol.23465826593Needs assessment of primary care physicians in the management ofchronic pain in cancer survivorsR.ChowK.SaundersH.BurkeA.BelangerE.ChowSupport Care Cancer1135053514Effective delivery of palliative radiotherapy: A prospectivestudyA.Clément-ZhaoM.LuuJE.BibaultC.DaveauS.KrepsH.JaulmesB.Dessard-DianaM.HoussetP.GiraudC.DurduxCancer Radiother235365369