Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma

Version 1 : Received: 12 October 2023 / Approved: 13 October 2023 / Online: 16 October 2023 (08:36:49 CEST)

A peer-reviewed article of this Preprint also exists.

Marroncini, G.; Naldi, L.; Fibbi, B.; Errico, A.; Polvani, S.; Brogi, M.; Fanelli, A.; Maggi, M.; Peri, A. Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma. Int. J. Mol. Sci. 2023, 24, 16680. Marroncini, G.; Naldi, L.; Fibbi, B.; Errico, A.; Polvani, S.; Brogi, M.; Fanelli, A.; Maggi, M.; Peri, A. Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma. Int. J. Mol. Sci. 2023, 24, 16680.

Abstract

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 differ-ent tissues show a significantly increased proliferation rate and invasion potential, when cul-tured 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 inva-sivity of the neuroblastoma cell line SK-N-AS in hyponatremic vs. normonatremic mice. Ani-mals 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, chro-mogranin 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 in vivo demonstration that hyponatremia is associated to increased cancer growth by activating molecular mechanisms that promote proliferation, angiogenesis and invasivity.

Keywords

hyponatremia; Syndrome of Inappropriate Antidiuresis; cancer; neuroblastoma; murine xeno-graft

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.