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Vet. Sci. 2017, 4(2), 21;

Animal Models of Cancer-Associated Hypercalcemia

Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
Department of Pathology, Faculty of Veterinary Medicine, Benha University, Banha 13511, Egypt
Author to whom correspondence should be addressed.
Academic Editor: Ir. J. A. Jan Mol
Received: 11 December 2016 / Revised: 14 March 2017 / Accepted: 10 April 2017 / Published: 13 April 2017
(This article belongs to the Special Issue Comparative studies on Endocrine Diseases in Animals and Humans)
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Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone. Humoral hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the production and release of tumor-associated cytokines and humoral factors, such as parathyroid hormone-related protein (PTHrP), that act at distant sites to increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH) occurs when primary or metastatic bone tumors act locally by releasing factors that stimulate osteoclast activity and bone resorption. LOH is a less frequent cause of CAH and in some cases can induce hypercalcemia in concert with HHM. Rarely, ectopic production of parathyroid hormone has been described. PTHrP-mediated hypercalcemia is the most common mechanism of CAH in human and canine malignancies and is recognized in other domestic species. Spontaneous and experimentally-induced animal models have been developed to study the mechanisms of CAH. These models have been essential for the evaluation of novel approaches and adjuvant therapies to manage CAH. This review will highlight the comparative aspects of CAH in humans and animals with a discussion of the available animal models used to study the pathogenesis of this important clinical syndrome. View Full-Text
Keywords: hypercalcemia; paraneoplastic syndrome; cat; comparative oncology; dog; HHM; PTHrP; bone metastasis hypercalcemia; paraneoplastic syndrome; cat; comparative oncology; dog; HHM; PTHrP; bone metastasis

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Kohart, N.A.; Elshafae, S.M.; Breitbach, J.T.; Rosol, T.J. Animal Models of Cancer-Associated Hypercalcemia. Vet. Sci. 2017, 4, 21.

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