Findings of this study were presented in part at the 24th Annual Veterinary Cancer Society Conference, Kansas City, MO, 2004; the 25th Annual Veterinary Cancer Society Conference, Huntington Beach, CA, 2005; and the 26th Annual Veterinary Cancer Society Conference, Pine Mountain, GA, 2006.
In Vivo and In Vitro Efficacy of Zoledronate for Treating Oral Squamous Cell Carcinoma in Cats
Version of Record online: 14 FEB 2008
Copyright © 2008 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 22, Issue 1, pages 158–163, January–February 2008
How to Cite
Wypij, J.M., Fan, T.M., Fredrickson, R.L., Barger, A.M., De Lorimier, L.P. and Charney, S.C. (2008), In Vivo and In Vitro Efficacy of Zoledronate for Treating Oral Squamous Cell Carcinoma in Cats. Journal of Veterinary Internal Medicine, 22: 158–163. doi: 10.1111/j.1939-1676.2007.0010.x
This study was conducted at the Comparative Oncology Research Laboratory.
- Issue online: 14 FEB 2008
- Version of Record online: 14 FEB 2008
- Submitted February 24, 2007; Revised May 7, July 7, 2007; Accepted August 9, 2007.
- Focal malignant osteolysis;
- Serum C-telopeptide;
- Soluble vascular endothelial growth factor
Background: Feline oral squamous cell carcinoma (OSCC) may cause painful bone destruction. Given the local invasiveness and rapid clinical progression of OSCC, conventional therapies are often palliative. In human cancer patients, zoledronate exerts anticancer effects by inhibiting tumor-induced angiogenesis and malignant osteolysis.
Hypothesis: Zoledronate will exert in vitro and in vivo anti-angiogenic and antiresorptive effects in feline OSCC.
Animals: Eight cats with OSCC were prospectively treated with zoledronate and conventional treatment modalities.
Methods: In vitro, zoledronate's effects in modulating soluble vascular endothelial growth factor (VEGF) secretion and receptor activator of nuclear factor kB (NF-κB) ligand (RANKL) expression were investigated in a feline OSCC cell line (SCCF1). In vivo, basal serum C-telopeptide (CTx) concentrations were compared among normal and OSCC-bearing cats, and the biologic effects of zoledronate administration in cats with naturally occurring OSCC were quantified by serially assessing circulating serum VEGF and CTx concentrations.
Results: In vitro, zoledronate concentrations greater than 3 μM reduce soluble VEGF secretion in the SCCF1 cell line. The expression of RANKL in the SCCF1 cell line was also modulated by zoledronate, with low concentrations (3 μM) decreasing but higher concentrations (30 μM) increasing RANKL expression in comparison with untreated cells. In vivo, cats with bone-invasive OSCC had greater serum CTx concentrations in comparison with geriatric, healthy controls. Treatment with zoledronate rapidly decreased circulating serum VEGF and CTx concentrations in cats with spontaneously occurring OSCC.
Conclusions and Clinical Importance: Zoledronate exerts in vitro and in vivo effects that may favor the slowing of tumor growth and pathologic bone turnover associated with OSCC.