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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2345-2353
Number of pages9
JournalOncology Reports
Volume33
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Vascular Endothelial Growth Factor A
Canidae
Breast Neoplasms
Dogs
Neoplasms
Serum
Gene Expression
Breast
Oxygen
Neoplasm Metastasis
Immunosorbents
Control Groups
Genes
Blood Vessels
Real-Time Polymerase Chain Reaction
Endothelial Cells
Lymph Nodes
Enzyme-Linked Immunosorbent Assay

Keywords

  • Angiogenesis
  • Canine mammary tumors
  • Hypoxiainducible factor-1α
  • Prognostic markers
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Moschetta, M. G., Maschio, L. B., Jardim-Perassi, B. V., Gelaleti, G. B., Lopes, J. R., Leonel, C., ... De Campos Zuccari, D. A. P. (2015). Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors. Oncology Reports, 33(5), 2345-2353. https://doi.org/10.3892/or.2015.3856

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; Do Nascimento Goncalves, Naiane; Ferreira, Livia Carvalho; Martins, Gustavo Rodrigues; Borin, Thaiz Ferraz; De Campos Zuccari, Debora Aparecida Pires.

In: Oncology Reports, Vol. 33, No. 5, 01.05.2015, p. 2345-2353.

Research output: Contribution to journalArticle

Moschetta, MG, Maschio, LB, Jardim-Perassi, BV, Gelaleti, GB, Lopes, JR, Leonel, C, Do Nascimento Goncalves, N, Ferreira, LC, Martins, GR, Borin, TF & De Campos Zuccari, DAP 2015, 'Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors', Oncology Reports, vol. 33, no. 5, pp. 2345-2353. https://doi.org/10.3892/or.2015.3856
Moschetta MG, Maschio LB, Jardim-Perassi BV, Gelaleti GB, Lopes JR, Leonel C et al. Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors. Oncology Reports. 2015 May 1;33(5):2345-2353. https://doi.org/10.3892/or.2015.3856
Moschetta, Marina Gobbe ; Maschio, Larissa Bazela ; Jardim-Perassi, Bruna Victorasso ; Gelaleti, Gabriela Bottaro ; Lopes, Juliana Ramos ; Leonel, Camila ; Do Nascimento Goncalves, Naiane ; Ferreira, Livia Carvalho ; Martins, Gustavo Rodrigues ; Borin, Thaiz Ferraz ; De Campos Zuccari, Debora Aparecida Pires. / Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors. In: Oncology Reports. 2015 ; Vol. 33, No. 5. pp. 2345-2353.
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