Djamgoz Mustafa B A
Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, London, United Kingdom.
Biotechnology Research Centre, Cyprus International University, Lefkosa, North Cyprus.
Bioelectricity. 2020 Mar 1;2(1):14-20. doi: 10.1089/bioe.2019.0035. Epub 2020 Mar 18.
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.
低钠血症是指血清钠水平低于135 mmol/L的现象，在癌症患者中很常见，并且与预后不良相关。传统上，低钠血症被归因于“抗利尿激素分泌不当综合征”，导致液体潴留时间延长。然而，这不太可能是唯一的机制。在本研究中，我们提出一个假说：癌症过程中各种钠转运蛋白的上调对癌症相关低钠血症的病理生理学有重大贡献。此类钠转运蛋白包括电压门控钠通道，尤其是其缺氧促进的持续电流、上皮钠通道和瞬时受体电位通道。因此，低钠血症继发于癌症，即血清水平下降是由于癌细胞从细胞外液摄取钠所致。事实上，癌细胞/组织的钠含量高于正常水平。反过来，细胞内钠浓度的升高会带来一系列细胞效应，包括促进侵袭性的细胞外酸化，从而导致预后不良。这一观点为癌症及相关低钠血症提供了新的治疗方法。
