title: Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer.
abstract: Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and fatal types of mammary cancer, and both have a very poor prognosis and low survival rate. Human IBC is characterised by exacerbated angiogenesis, lymphangiogenesis, and lymphangiotropism. Lymphangiotropism is also characteristic of IMC, but microvascular density (MVD) and lymphangiogenesis have not been previously studied in canine IMC. In this study immunohistochemical expression of several angiogenesis-related factors (cyclooxygenase [COX]-2, vascular endothelial growth factors A and D [VEGF-A, VEGF-D], and vascular endothelial growth factor receptor 3 [VEGFR-3]), MVD, lymphatic proliferation index (LPI), and Ki-67 tumour proliferation index (PI) were studied in 21 canine IMC samples, 20 canine high-grade malignant non-IMC mammary tumours (MMTs), and four normal mammary gland samples (NMGs). All mammary neoplasms were histologically categorised as grade III. COX-2 values were also analysed by RT-PCR in seven IMCs, six MMTs and four NMGs. The expressions of COX-2, VEGF-A, and VEGF-D were significantly higher in IMC, MVD and LPI tumours, but not PI. In MMTs, COX-2 immunoexpression was significantly associated with VEGF-A, while in IMCs COX-2 was associated with VEGF-D (lymphangiogenic factor), its receptor VEGFR-3, and LPI. These results suggested that lymphangiogenic pathway stimulation isa specific role of COX-2 in IMC angiogenesis, which justifies the use of COX-2-based targeted palliative therapies in dogs. The exacerbated angiogenesis and lymphangiogenesis and the increased expression of angiogenesis-related factors further support canine IMC as a natural model for the study of human IBC.
authors.affiliation: Department of Animal Medicine, Surgery and Pathology. Veterinary School, Complutense University of Madrid, 28040 Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Clemente
authors.forename: Ana Rodríguez
authors.initials: AR
authors.lastname: Sánchez-Archidona
authors.forename: David
authors.initials: D
authors.lastname: Sardón
authors.forename: Lucía
authors.initials: L
authors.lastname: Díez
authors.forename: Asunción
authors.initials: A
authors.lastname: Martín-Ruiz
authors.forename: Sara
authors.initials: S
authors.lastname: Caceres
authors.forename: Francesco
authors.initials: F
authors.lastname: Sassi
authors.forename: M
authors.initials: M
authors.lastname: Dolores Pérez-Alenza
authors.forename: Juan C
authors.initials: JC
authors.lastname: Illera
authors.forename: Susana
authors.initials: S
authors.lastname: Dunner
authors.forename: Laura
authors.initials: L
authors.lastname: Peña
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D007249:Inflammation / Q000662:veterinary*; D042583:Lymphangiogenesis / Q000502:physiology; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D051546:Cyclooxygenase 2; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Angiogenesis; COX-2; Canine mammary cancer; Dog; Inflammatory breast cancer