Stem cell growth factor receptor in canine vs. feline osteosarcomas

Abstract

Osteosarcoma is considered the most common bone cancer in cats and dogs, with cats having a much better prognosis than dogs, since the great majority of dogs with osteosarcoma develop distant metastases. In search of a factor possibly contributing to this disparity, the stem cell growth factor receptor KIT was targeted, and the messenger (m)RNA and protein expression levels of KIT were compared in canine vs. feline osteosarcomas, as well as in normal bone. The mRNA expression of KIT was quantified by reverse transcription-quantitative polymerase chain reaction, and was observed to be significantly higher in canine (n=14) than in feline (n=5) osteosarcoma samples (P<0.001). KIT protein expression was evaluated by immunohistochemistry, which revealed that 21% of canine osteosarcoma samples did not exhibit KIT staining in their neoplastic cells, while in 14% of samples, a score of 1 (<10% positive tumour cells) was observed, and in 50% and 14% of samples, a score of 2 (10–50% positivity) and 3 (>50% positivity), respectively, was observed. By contrast, the cancer cells of all the feline bone tumour samples analysed were entirely negative for KIT. Notably, canine and feline osteocytes of healthy bone tissue lacked any KIT expression. These results could be the first evidence that KIT may be involved in the higher aggressiveness of canine osteosarcoma compared with feline osteosarcoma.

Genetic alterations of KIT during clonal expansion and subsequent acquisition of resistance to toceranib in a canine mast cell tumor cell line

“…The HEK293 cells then were lysed with cell lysis buffer (#9803, Cell Signaling Technology). Aliquots of the lysates were subjected to Western blot analysis using polyclonal rabbit anti‐human CD117 antibody (A4502; Dako), a reagent that previously has been used for detection of canine KIT (Wolfesberger et al, ), or using monoclonal rabbit anti‐human phospho‐c‐Kit (Tyr703) antibody (3073S; Cell Signaling Technology), a reagent that previously has been used for detection of canine phosphorylated KIT (Kobayashi et al, ), followed by incubation with horseradish peroxidase‐conjugated donkey anti‐rabbit IgG whole antibody (GE Healthcare). Immunoreactive bands were visualized using an ECL Prime (GE Healthcare) and a LAS‐4000 (Fujifilm).…”

Genomics and transcriptomics in veterinary oncology (Review)

“…The study detected EPO-R expression in canine and feline tumor samples, but suggested only a minimal role for EPO-R in tumor development in both species ( 19 ). The expression of stem cell growth factor receptor KIT, quantified by RT-qPCR and immunohistochemistry, was observed to be significantly higher in canine than in feline osteosarcoma samples, indicating that it may be involved in the higher aggressiveness of canine osteosarcoma compared with feline osteosarcoma ( 20 ).…”

“…In the last decade, transcriptomics has also served a role in canine and human osteosarcoma research. Two studies ( 19 , 20 ) employed RT-qPCR to determine the differential expression of genes, one of which ( 19 ) assessed erythropoietin receptor (EPO-R) gene expression in canine and feline osteosarcomas. While both dogs and cats develop osteosarcoma, the occurrence of metastasis is vastly different between the two species, with the canine form frequently exhibiting metastasis (80–90%) while the feline form is rarely (5–10%) metastatic ( 21 ).…”

S100A4 mRNA-protein relationship uncovered by measurement noise reduction

“…2). Next, we compared the transcriptional stability of several normalizers that were formerly recommended for use in canine osteosarcoma without transcriptome-wide expression profiling for this context such as OAZ1 [16] or B2M, HNRNPH, RPS5 and RPS19 [17] ( Table S5). This set consisted of classical normalizers that were derived from educated guesswork (e.g.…”