Expression of receptor tyrosine kinase targets PDGFR-β, VEGFR2 and KIT in canine transitional cell carcinoma
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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
L Walters1, O Martin1, J Price2
1Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee.
Abstract:
Transitional cell carcinoma (TCC) is the most common neoplasia of the canine urinary tract. It tends to be locally invasive and has a moderate metastatic rate. Receptor tyrosine kinases (RTKs) play an important role in promoting cell growth, differentiation and regulation of cell function. RTK inhibitor toceranib phosphate has been used anecdotally to treat TCC. The goal of this study was to evaluate archived normal urinary bladder, TCC and cystitis bladder samples for expression of toceranib phosphate targets: VEGFR2, PDGFR-β and stem cell factor receptor (KIT). A significant number of TCC samples expressed PDGFR-β compared with cystitis and normal bladder samples (P<.0001). While all the tumour samples stained positively for VEGFR2, there was no significant difference between tumour, cystitis and normal bladder samples in intensity scores or staining distribution. Minimal positive staining for KIT was noted in the tumour samples. Based on this proof of target study, further investigation is warranted to determine clinical response of TCC to toceranib phosphate.
Insights
Transitional cell carcinoma (TCC) in dogs often expresses PDGFR-β, a target of toceranib phosphate. This suggests potential efficacy of this receptor tyrosine kinase inhibitor for canine TCC treatment.
Area of Science:
- Veterinary Oncology
- Molecular Biology
- Cancer Research
Background:
- Transitional cell carcinoma (TCC) is the most common canine urinary tract cancer.
- Receptor tyrosine kinases (RTKs) are crucial for cell growth and regulation.
- Toceranib phosphate, an RTK inhibitor, is anecdotally used for TCC treatment.
Purpose of the Study:
- To evaluate the expression of toceranib phosphate targets in canine urinary bladder samples.
- To assess the expression of VEGFR2, PDGFR-β, and KIT in normal, cystitis, and TCC bladder tissues.
Main Methods:
- Archived samples of normal canine urinary bladder, TCC, and cystitis were analyzed.
- Immunohistochemistry was used to detect the expression of VEGFR2, PDGFR-β, and KIT.
- Staining intensity and distribution were evaluated.
Main Results:
- A significant number of TCC samples showed PDGFR-β expression compared to normal and cystitis samples (P<.0001).
- All TCC samples stained positively for VEGFR2, with no significant difference in intensity or distribution across sample types.
- Minimal KIT expression was observed in TCC samples.
Conclusions:
- PDGFR-β is significantly expressed in canine TCC, indicating it as a potential therapeutic target.
- VEGFR2 and KIT expression warrants further investigation in the context of TCC treatment.
- Further studies are needed to confirm the clinical efficacy of toceranib phosphate for canine TCC.
