Expression of Voltage-Gated Sodium Channel Na_v1.8 in Human Prostate Cancer is Associated with High Histological Grade

Voltage-gated sodium (Na_v) channels are required for impulse conductance in excitable tissues. Na_vs have been linked to human cancers, including prostate. The expression and distribution of Na_v isoforms (Na_v1.1-Na_v1.9) in human prostate cancer are not well established. Here, we evaluated the expression of these isoforms and investigated the expression of Na_v1.8 in human prostate cancer tissues. Na_v1.8 was highly expressed in all examined cells. Expression of Na_v1.1, Na_v1.2, and Na_v1.9 were high in DU-145, PC-3 and PC-3M cells compared to LNCaP (hormone-dependent), C4-2, C4-2B, and CWR22Rv-1 cells. Na_v1.5 and Na_v1.6 were expressed in all cells examined. Na_v1.7 expression was absent in PC-3M and CWR22Rv-1, but expressed in the other cells examined. Immunohistochemistry revealed intensive Na_v1.8 staining correlated with more advanced pathologic stage of disease. Increased intensity of nuclear Na_v1.8 correlated with increased Gleason grade. Our results revealed that Na_v1.8 is universally expressed in human prostate cancer cells. Na_v1.8 expression statistically correlated with pathologic stage (P=0.04) and Gleason score (P=0.01) of human prostate tissue specimens. The aberrant nuclear localization of Na_v1.8 with advanced prostate cancer tissues warrant further investigation into use of Na_v1.8 as a potential biomarker to differentiate between early and advanced disease.