학술논문
Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma.
Document Type
Academic Journal
Author
Marroncini G; Endocrinology, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, AOU Careggi, 50139 Florence, Italy.; Naldi L; Endocrinology, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, AOU Careggi, 50139 Florence, Italy.; Fibbi B; Endocrinology, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, AOU Careggi, 50139 Florence, Italy.; Pituitary Diseases and Sodium Alterations Unit, Careggi University Hospital, 50139 Florence, Italy.; Errico A; Endocrinology, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, AOU Careggi, 50139 Florence, Italy.; Polvani S; Gastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, 50139 Florence, Italy.; Brogi M; Central Laboratory, Careggi University Hospital, 50139 Florence, Italy.; Fanelli A; Central Laboratory, Careggi University Hospital, 50139 Florence, Italy.; Maggi M; Endocrinology, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, AOU Careggi, 50139 Florence, Italy.; Peri A; Endocrinology, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, AOU Careggi, 50139 Florence, Italy.; Pituitary Diseases and Sodium Alterations Unit, Careggi University Hospital, 50139 Florence, Italy.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Subject
Language
English
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 mm 3 , 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.