VEGFR-2: potencial alvo terapêutico nos tumores de mama da cadela

Investigadores do Instituto de Ciências Biomédicas de Abel Salazar da Universidade do Porto demonstraram que o VEGFR-2, o principal receptor ativado pelo VEGF durante a angiogénese, se encontra amplamente expresso nos carcinossarcomas mamários caninos, um tipo de tumor raro tanto na cadela como na mulher. Este resultado reforça o papel dos tumores mamários espontâneos em cães como modelo de estudo de tumores menos frequentes na mulher.

Autores e Afiliações:

Santos, A.¹, Lopes, C.², Gärtner, F.^2,3, Matos, A.J.F.^4,5

1 – Faculty of Veterinary Medicine of University Lusófona of Humanites and Technologies, Lisbon, Portugal

2 - Department of Molecular Pathology and Immunology of the Biomedical Sciences Institute of Abel Salazar (ICBAS), University of Porto, Portugal

3 - Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal

4 - Department of Veterinary Clinics of the Biomedical Sciences Institute of Abel Salazar (ICBAS), University of Porto, Portugal

5 - Animal Science and Study Centre / Food and Agrarian Sciences and Technologies Institute (CECA/ICETA), University of Porto, Portugal

Abstract:

Vascular endothelial growth factor receptor-2 (VEGFR-2) is the main receptor activated by vascular endothelial growth factor -A (VEGF-A) to promote tumour angiogenesis. Its clinical prognostic value has not been studied in canine mammary tumours (CMTs). Dogs with mammary cancer were enrolled in a survival study and the immunohistochemical expressions of VEGFR-2 and VEGF-A were analysed and associated with clinicopathological features. VEGFR-2 expression was associated with VEGF immunoreactivity in cancer cells, supporting the presence of an autocrine loop that may be involved in CMTs growth and survival. VEGFR-2 was also expressed by endothelial cells from tumour vasculature and positively associated with stromal matrix metalloproteinase-9 (MMP-9), suggesting the existence of a link between endothelial cells activation and up-regulation of matrix degrading proteins. Carcinosarcomas exhibited high VEGFR-2 expression suggesting that it may be one of the activated molecular pathways in this aggressive histological type and that VEGFR-2 inhibitors may constitute a potential treatment to improve the prognosis of these patients. Both VEGF and VEGFR-2 immunoreactivities were independent of patients' overall survival (OS) and disease-free survival (DFS).

Revista: Veterinary Comparative Oncology, 2014

Link: http://onlinelibrary.wiley.com/doi/10.1111/vco.12107/abstract