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Matrix metalloproteinases and their inhibitors in canine mammary tumors

Luca Aresu1*, Mery Giantin1, Emanuela Morello2, Marta Vascellari3, Massimo Castagnaro1, Rosa Lopparelli1, Vanessa Zancanella1, Anna Granato3, Spiridione Garbisa4, Arianna Aricò1, Alice Bradaschia4, Franco Mutinelli3 and Mauro Dacasto1

Author Affiliations

1 Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Padova, Padova, Italy

2 Dipartimento di Patologia Animale, Facoltà di Medicina Veterinaria, Università degli Studi di Torino, Italy

3 Histopathology Department, Istituto Zooprofilattico Sperimentale delle Venezie, Viale dell'Università 10, 35020 Legnaro (PD), Italy

4 Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, viale Colombo 3, Padova, Italy

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BMC Veterinary Research 2011, 7:33  doi:10.1186/1746-6148-7-33

Published: 4 July 2011



Malignant canine mammary tumors represent 50% of all neoplasms in female dogs. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression, and they are also associated with the reactive stroma, which provides structural and vascular support for tumor growth.


MMP-2, MMP-9 and MT1-MMP were expressed at both the mRNA and protein levels in tumor samples. MMP-2 and MMP-9 immunohistochemical reactions were evident both in the epithelial tumor cells and in the stromal compartment to varying degrees; in particular, the intensity of the MMP-2 staining was stronger in the stromal fibroblasts close to epithelial tumor cells in simple carcinomas than in adenomas. These data were supported by gelatin-zymography; bands for the active form of MMP-2 were found in 94% of carcinoma samples, compared with 17% of benign tumor samples. The gene expression and immunohistochemical results for MT1-MMP were comparable to those for MMP-2. The immunoreactivity for MMP-13 and TIMP-2 was lower in carcinomas than in adenomas, confirming the mRNA data for MMP-13 and the other MMP inhibitors that were evaluated. The active form of MMP-9, but not the active form of MMP-2, was identified in the plasma of all of the tested dogs.


Our findings suggest that MMP-9, MMP-2 and MT1-MMP, which are synthesized by epithelial cancer cells and cancer-associated fibroblasts, play an important role in malignant canine mammary tumors. The reduction of MMP-13 and TIMP-2 could also be a significant step in malignant transformation. MMP-2 and MT1-MMP could be further evaluated as future biomarkers for predicting the progression and prognosis of canine mammary tumors.