Abnormal sodium‐potassium dynamics and Na,K‐ATPase expression in Mel‐290 uveal melanoma cells.

Abstract

Uveal melanoma is the most common form of malignant intraocular tumor. Metastases are common and the mortality for metastatic uveal melanoma approaches 90 %. Here we report on abnormal sodium‐potassium dynamics in a particular uveal melanoma cell line, Mel‐290. The ratio of sodium concentration to potassium concentration in Mel‐290 cells, determined by atomic absorption spectrometry, was 0.57 compared to 0.1 in a different melanoma cell, OCM‐3, and 0.15 in pig ciliary epithelium. Assuming cell Na+K = 140 mM, Mel‐290 cells have resting sodium concentration of approx. 50 mM which is several fold higher than the concentration in normal cells. Western blot studies showed lower abundance of Na,K‐ATPase alpha 1 subunit protein in Mel‐290 compared to OCM‐3. Differences in Na,K‐ATPase alpha subunit phosphorylation also were observed. In contrast to Na,K‐ATPase, H/K‐ATPase beta subunit and H‐ATPase (v‐ATPase) beta subunit were higher in Mel‐290 compared to OCM‐3. A high Na:K ratio was detected in two other melanoma cell types, suggesting the possible existence of a high sodium sub‐group of melanomas. It remains to be determined whether the high‐sodium phenotype is related to a particular pattern of ATPase expression or regulation. It is noteworthy that high cytoplasmic sodium has been detected in certain liver, brain and breast tumors by MRI and other techniques.