In
cancer patients,
hyponatremia is detected in about 40% of cases at hospital admission and has been associated to a worse outcome. We have previously observed that
cancer cells from different tissues show a significantly increased proliferation rate and invasion potential, when cultured in low extracellular [Na+]. We have recently developed an animal model of
hyponatremia using Foxn1nu/nu mice. The aim of the present study was to compare
tumor growth and invasivity of the
neuroblastoma cell line SK-N-AS in hyponatremic vs. normonatremic mice. Animals were subcutaneously implanted with
luciferase-expressing SK-N-AS cells. When masses reached about 100 mm3,
hyponatremia was induced in a subgroup of animals via
desmopressin infusion.
Tumor masses were significantly greater in hyponatremic mice, starting from day 14 and until the day of sacrifice (day 28). Immunohistochemical analysis showed a more intense vascularization and higher levels of expression of the
proliferating cell nuclear antigen,
chromogranin A and
heme oxigenase-1 gene in hyponatremic mice. Finally,
metalloproteases were also more abundantly expressed in hyponatremic animals compared to control ones. To our knowledge, this is the first demonstration in an experimental animal model that
hyponatremia is associated to increased
cancer growth by activating molecular mechanisms that promote proliferation, angiogenesis and invasivity.