title: Matrix metalloproteinases and their inhibitors in canine mammary tumors.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Padova, Padova, Italy. luca.aresu@unipd.it
authors: Luca
authors: L
authors: Aresu
authors: Mery
authors: M
authors: Giantin
authors: Emanuela
authors: E
authors: Morello
authors: Marta
authors: M
authors: Vascellari
authors: Massimo
authors: M
authors: Castagnaro
authors: Rosa
authors: R
authors: Lopparelli
authors: Vanessa
authors: V
authors: Zancanella
authors: Anna
authors: A
authors: Granato
authors: Spiridione
authors: S
authors: Garbisa
authors: Arianna
authors: A
authors: Aricò
authors: Alice
authors: A
authors: Bradaschia
authors: Franco
authors: F
authors: Mutinelli
authors: Mauro
authors: M
authors: Dacasto
mesh_terms: D000818:Animals; D004273:DNA, Neoplasm / Q000378:metabolism; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14