Transcriptome of Two Canine Prostate Cancer Cells Treated With Toceranib Phosphate Reveals Distinct Antitumor Profiles Associated With the PDGFR Pathway

Autor(es)

Kobayashi, Priscila E. ^[1] ; Lainetti, Patricia F. ^[2] ; Leis-Filho, Antonio F. ^[1] ; Delella, Flavia K. ^[3] ; Carvalho, Marcio ^[1] ; Cury, Sarah Santiloni ^[3] ; Carvalho, Robson Francisco ^[3] ; Fonseca-Alves, Carlos E. ^{[2, 4]} ; Laufer-Amorim, Renee ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ Unesp, Dept Vet Clin, Sch Vet Med & Anim Sci, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Vet Med & Anim Sci, Dept Vet Surg & Anesthesiol, Botucatu, SP - Brazil

^[3] Sao Paulo State Univ Unesp, Dept Morphol, Inst Biosci, Botucatu, SP - Brazil

^[4] Paulista Univ UNIR, Inst Hlth Sci, Bauru, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN VETERINARY SCIENCE; v. 7, NOV 26 2020.
• Citações Web of Science: 0

Resumo

Canine prostate cancer (PC) presents a poor antitumor response, usually late diagnosis and prognosis. Toceranib phosphate (TP) is a nonspecific inhibitor of receptor tyrosine kinases (RTKs), including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-KIT. This study aimed to evaluate VEGFR2, PDGFR-beta, and c-KIT protein expression in two established canine PC cell lines (PC1 and PC2) and the transcriptome profile of the cells after treatment with TP. Immunofluorescence (IF) analysis revealed VEGFR2 and PDGFR-beta protein expression and the absence of c-KIT protein expression in both cell lines. After TP treatment, only the viability of PC1 cells decreased in a dose-dependent manner. Transcriptome and enrichment analyses of treated PC1 cells revealed 181 upregulated genes, which were related to decreased angiogenesis and cell proliferation. In addition, we found upregulated PDGFR-A, PDGFR-beta, and PDGF-D expression in PC1 cells, and the upregulation of PDGFR-beta was also observed in treated PC1 cells by qPCR. PC2 cells had fewer protein-protein interactions (PPIs), with 18 upregulated and 22 downregulated genes; the upregulated genes were involved in the regulation of parallel pathways and mechanisms related to proliferation, which could be associated with the resistance observed after treatment. The canine PC1 cell line but not the PC2 cell line showed decreased viability after treatment with TP, although both cell lines expressed PDGFR and VEGFR receptors. Further studies could explain the mechanism of resistance in PC2 cells and provide a basis for personalized treatment for dogs with PC. (AU)

• Processo FAPESP: 15/25400-7 - Estudo para caracterização in vitro e molecular de células prostáticas caninas e avaliação da resposta antitumoral a drogas alvo dirigidas
• Beneficiário: Carlos Eduardo Fonseca Alves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado