In vivo and in vitro efficacy of zoledronate for treating oral squamous cell carcinoma in cats.
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.


OBJECTIVE
Zoledronate will exert in vitro and in vivo anti-angiogenic and antiresorptive effects in feline OSCC.


METHODS
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 kappaB (NF-kappaB) 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 microM 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 microM) decreasing but higher concentrations (30 microM) 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
Zoledronate exerts in vitro and in vivo effects that may favor the slowing of tumor growth and pathologic bone turnover associated with OSCC.
Wypij
J M
JM
Comparative Oncology Research Laboratory, Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, IL 61802, USA.
Fan
T M
TM
Fredrickson
R L
RL
Barger
A M
AM
de Lorimier
L P
LP
Charney
S C
SC
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000662:veterinary*; D002415:Cats; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D010455:Peptides / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid