Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors

Moschetta,Marina Gobbe; Maschio,Larissa Bazela; Jardim-Perassi,Bruna Victorasso; Gelaleti,Gabriela Bottaro; Lopes,Juliana Ramos; Leonel,Camila; Gonçalves,Naiane Do Nascimento; Ferreira,Lívia Carvalho; Martins,Gustavo Rodrigues; Borin,Thaiz Ferraz; Zuccari,Debora Aparecida Pires De Campos

doi:10.3892/or.2015.3856

Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors

Authors:
- Marina Gobbe Moschetta
- Larissa Bazela Maschio
- Bruna Victorasso Jardim-Perassi
- Gabriela Bottaro Gelaleti
- Juliana Ramos Lopes
- Camila Leonel
- Naiane Do Nascimento Gonçalves
- Lívia Carvalho Ferreira
- Gustavo Rodrigues Martins
- Thaiz Ferraz Borin
- Debora Aparecida Pires De Campos Zuccari
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Affiliations: PostGraduate Program in Health Sciences, Faculty of Medicine of Sao Jose do Rio Preto/FAMERP, São José do Rio Preto, SP, Brazil, Laboratory of Cancer Molecular Investigation (LIMC), Faculty of Medicine of Sao Jose do Rio Preto/FAMERP, São José do Rio Preto, SP, Brazil
Published online on: March 16, 2015 https://doi.org/10.3892/or.2015.3856
Pages: 2345-2353

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Abstract

Mammary tumors are the most common type of tumor in dogs, with approximately half of these tumors being malignant. Hypoxia, characterized by oxygen levels below normal, is a known adverse factor to cancer treatment. The hypoxia-inducible factor 1α (HIF-1α) is a central regulator of the pathophysiological response of mammalian cells to low oxygen levels. HIF-1α activates the transcription of vascular endothelial growth factor (VEGF), which in turn promotes angiogenesis through its ability to stimulate the growth, migration and invasion of endothelial cells to form new blood vessels, contributing to tumor progression. In this study, we evaluated the serum concentration and gene expression of VEGF and HIF-1α linking them with clinicopathological parameters and survival of dogs with mammary tumors in order to infer the possible prognostic value of these factors. We collected blood and tumor fragments of 24 female dogs with malignant mammary tumors (study group) and 26 non-affected female dogs (control group) to verify the gene expression of VEGF and HIF-1α by quantitative real-time PCR (qPCR) and the serum levels by ELISA (enzyme-linked immunosorbent). The results showed high serum levels of VEGF in the study group and its correlation between abundant vascularization, lymph node involvement, metastasis, death rate and low survival (p<0.05). The serum percentage of HIF-1α in female dogs with mammary neoplasia was lower than that in the control group and higher in female dogs with tumor metastasis and history of tumor recurrence (p<0.05). Regarding gene expression, there was a gene overexpression of VEGFA in female dogs with poor outcome, in contrast to the gene underexpression of HIF-1A. Taken together, these results suggested that VEGF is important in tumor progression and can be used as a potential prognostic marker in the clinic and may be useful in predicting tumor progression in dogs with mammary neoplasia.

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