Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer

Autor(es)

Leis-Filho, Antonio Fernando ^[1] ; Lainetti, Patricia deFaria ^[1] ; Kobayashi, Priscila Emiko ^[2] ; Palmieri, Chiara ^[3] ; Amorim, Renee Laufer ^[2] ; Fonseca-Alves, Carlos Eduardo ^{[4, 1]}

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Sch Vet Med & Anim Sci, Dept Vet Surg & Anesthesiol, UNESP, BR-18618681 Botucatu, SP - Brazil

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

^[3] Univ Queensland, Sch Vet Sci, Gatton Campus, Gatton, Qld - Australia

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

• Tipo de documento: Artigo Científico
• Fonte: PROSTATE; v. 81, n. 14 JUL 2021.
• Citações Web of Science: 0

Resumo

Background Vascular endothelial growth factor-A (VEGF-A) and its receptor, VEGF receptor-2 (VEGFR-2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF-A/VEGFR-2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF-A and VEGFR-2 in canine prostate cancer (PC). Methods We analyzed VEGF-A and VEGFR-2 expression in 87 PC samples by immunohistochemistry and quantitative-polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF-A and VEGFR-2 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of VEGF-A and VEGFR-2 between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species. Results Negative to weakly positive expression levels of VEGF-A and VEGFR-2 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF-A (p < .0001) and VEGFR-2 (p < .0001) compared to NP. Moreover, positive correlations between the expression levels of VEGF-A and VEGFR-2 (Spearman's coefficient (r) = .68, p = .013) and the expression levels of VEGF-A and VEGFR-2 proteins (r = .8, p < .0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR-2 expression levels experienced a shorter survival period (p = .0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the VEGF-A and VEGFR-2 exhibited high homology between humans and dogs, and identified their protein structures in both species. Conclusions In conclusion, VEGFR-2 appears to be an independent prognostic factor in animals with PC. VEGF-A and VEGFR-2 are highly conserved between humans and dogs, which can be investigated further in future cross-species studies to explore their therapeutic applications. (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