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

Author(s):Show less -

Moschetta, Marina Gobbe ^{[1, 2]} ; Maschio, Larissa Bazela ^{[2, 3]} ; Jardim-Perassi, Bruna Victorasso ^{[2, 3]} ; Gelaleti, Gabriela Bottaro ^{[2, 3]} ; Lopes, Juliana Ramos ^{[2, 3]} ; Leonel, Camila ^{[2, 3]} ; Goncalves, Naiane Do Nascimento ^{[2, 1]} ; Ferreira, Livia Carvalho ^{[2, 3]} ; Martins, Gustavo Rodrigues ^{[2, 1]} ; Borin, Thaiz Perraz ^{[2, 1]} ; Pires De Campos Zuccari, Debora Aparecida ^{[2, 4, 5]}

Affiliation

^[1] Fac Med Sao Jose do Rio Preto FAMERP, PostGrad Program Hlth Sci, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Fac Med Sao Jose do Rio Preto FAMERP, Lab Canc Mol Invest LIMC, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[3] Sao Paulo State Univ Julio de Mesquita Filho UNES, PostGrad Program Genet, Sao Jose Do Rio Preto, SP - Brazil

^[4] Dept Mol Biol FAMERP, Sao Jose Do Rio Preto, SP - Brazil

^[5] Program PostGrad Genet UNESP IBILCE, Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: ONCOLOGY REPORTS; v. 33, n. 5, p. 2345-2353, MAY 2015.
• Web of Science Citations: 4

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 1 alpha(HIP-1 alpha) is a central regulator of the pathophysiological response of mammalian cells to low oxygen levels. HIF-1 alpha 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 HIP-1 alpha 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-1 alpha 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-1 alpha 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 HIP-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. (AU)

• FAPESP's process: 09/14883-6 - Detection of potential prognostic and preditive markers in canine mammary cancer
• Grantee: Debora Aparecida Pires de Campos Zuccari
• Support type: Regular Research Grants
• FAPESP's process: 10/13977-4 - Evaluation of new prognostic and predictive markers in mammary neoplasia of female dogs: serum and molecular assessment of VEGF and HIF-1
• Grantee: Marina Gobbe Moschetta
• Support type: Scholarships in Brazil - Master