Hyponatremia and Cancer Progression: Possible Association with Sodium-Transporting Proteins

Hyponatremia, the phenomenon of serum sodium level falling below 135 mmol/L, is seen frequently in cancer patients and has been correlated with poor prognosis. Hyponatremia has classically been attributed to the "syndrome of inappropriate antidiuretic hormone secretion," leading to prolonged fluid retention. However, this is unlikely to be the only mechanism. In this study, we advance the hypothesis that upregulation of various sodium-transporting proteins during the cancer process makes a significant contribution to the pathophysiology of cancer-associated hyponatremia. Such sodium-transporting proteins include voltage-gated sodium channels, especially its hypoxia-promoted persistent current, epithelial sodium channels, and transient receptor potential channels. Thus, hyponatremia follows cancer, whereby drop in blood serum level occurs as a result of uptake of sodium from extracellular fluid by cancer cells. Indeed, the sodium content of cancer cells/tissues is higher than normal. In turn, the rise in the intracellular sodium concentration brings about a range of cellular effects, including extracellular acidification that promotes invasiveness and thus leads to poor prognosis. This perspective offers novel therapies for cancer and the associated hyponatremia.