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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 6
[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
Total Affiliations: 4
Document type: Journal article
Source: PROSTATE; v. 81, n. 14 JUL 2021.
Web of Science Citations: 0

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)

FAPESP's process: 15/25400-7 - In vitro and molecular characterization of canine prostatic cells and evaluation of antitumor response against target drugs
Grantee:Carlos Eduardo Fonseca Alves
Support type: Scholarships in Brazil - Post-Doctorate