Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma
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Published:2023-11-23
Issue:23
Volume:24
Page:16680
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Marroncini Giada1ORCID, Naldi Laura1, Fibbi Benedetta12, Errico Alice1, Polvani Simone3, Brogi Marco4ORCID, Fanelli Alessandra4, Maggi Mario1ORCID, Peri Alessandro12ORCID
Affiliation:
1. Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, 50139 Florence, Italy 2. Pituitary Diseases and Sodium Alterations Unit, Careggi University Hospital, 50139 Florence, Italy 3. Gastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy 4. Central Laboratory, Careggi University Hospital, 50139 Florence, Italy
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 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.
Funder
Italian University and Research Ministry, PRIN
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference40 articles.
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