Comparison of Biomarkers Between Hepatic Tumors in Rat Models and a Dog

In Vivo. 2023 Jan-Feb;37(1):252-261. doi: 10.21873/invivo.13075.

Abstract

Background/aim: N1S1 rat models are commonly used in human medicine to study hepatocellular carcinoma (HCC). However, their use in veterinary medicine has not been reported. Thus, the aim of this study was to investigate whether the N1S1 rat models could be used to study canine HCC.

Materials and methods: The animals were divided into four groups: normal rat, N1S1 rat, normal dog, and HCC dog. Liver tissues of all animals were evaluated for vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β, and c-kit by immunohistochemistry. Slides of each factor were scored according to the percentage of stained tumor cells and intensity of the staining.

Results: Scores of VEGF and c-kit were high both in the tumor groups (the N1S1 rat and HCC dog groups) and the normal groups of dogs and rats. PDGFR-α was lower in the N1S1 rat group than that in the normal rat group (p=0.0042). It was also lower in the HCC dog group compared to the normal dog group (p=0.0008). PDGFR-β was higher in the HCC dog group than that in the normal dog group (p=0.0023) but was not detectable in the rat groups. EGFR was not detectable in any group.

Conclusion: Based on immunochemistry results, PDGFR-α and PDGFR-β can be used as biomarkers of canine HCC. Because PDGFR-α showed consistency between rats and dogs, it can be used for studying canine HCC.

Keywords: Hepatocellular carcinoma; N1S1 rat models; immunohistochemistry; tyrosine kinases.

MeSH terms

  • Animals
  • Biomarkers
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / veterinary
  • Dog Diseases / pathology
  • Dogs
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / veterinary
  • Proto-Oncogene Proteins c-kit / metabolism
  • Rats
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta
  • Vascular Endothelial Growth Factor A