Matrix metalloproteinase-2 and -9 involvement in canine tumors

Panayiotis Loukopoulos, Bruce A. Mungall, Rodney C. Straw, John R. Thornton , Wayne F. Robinson

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58 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) are a family of enzymes implicated in the degradation and remodeling of extracellular matrix and in vascularization. They are also involved in pathologic processes such as tumor invasion and metastasis in experimental cancer models and in human malignancies. We used gelatin zymography and immunohistochemistry to determine whether MMP-2 and MMP-9 are present in canine tumors and normal tissues and whether MMP production correlates with clinicopathologic parameters of prognostic importance. High levels of pro-MMP-9, pro-MMP-2, and active MMP-2 were detected in most canine tumors. Significantly higher MMP levels were measured in canine tumors than in nontumors, malignancies had higher MMP levels than benign tumors, and sarcomas had higher active MMP-2 than carcinomas. Cartilaginous tumors produced higher MMP levels than did nonsarcomatous malignancies, benign tumors, and normal tissues, and significantly greater MMP-2 than osteosarcomas and fibrosarcomas. Pro-MMP-9 production correlated with the histologic grade of osteosarcomas. The 62-kd form of active MMP-2 was detected only in high-grade, p53-positive, metastatic malignancies. Zymography proved to be a sensitive and quantitative technique for the assessment of MMP presence but has the limitation of requiring fresh tissue; immunohistochemistry is qualitative and comparatively insensitive but could be of value in archival studies. MMP presence was shown in a range of canine tumors, and their link to tumor type and grade was demonstrated for the first time. This study will allow a substantially improved evaluation of veterinary cancer patients and provides baseline information necessary for the design of clinical trials targeting MMPs.
Original languageEnglish
Article number12824510
Pages (from-to)382-94
Number of pages13
JournalVeterinary Pathology
Volume40
Issue number4
Publication statusPublished - 2003

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gelatinase A
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Canidae
metalloproteinases
neoplasms
dogs
Matrix Metalloproteinases
Neoplasms
gelatinase B
osteosarcoma
immunohistochemistry
Osteosarcoma
fibrosarcoma
Immunohistochemistry
sarcoma
gelatin
extracellular matrix
metastasis
carcinoma

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Loukopoulos, P., Mungall, B. A., Straw, R. C., Thornton , J. R., & Robinson, W. F. (2003). Matrix metalloproteinase-2 and -9 involvement in canine tumors. Veterinary Pathology, 40(4), 382-94. [12824510].
Loukopoulos, Panayiotis ; Mungall, Bruce A. ; Straw, Rodney C. ; Thornton , John R. ; Robinson, Wayne F. / Matrix metalloproteinase-2 and -9 involvement in canine tumors. In: Veterinary Pathology. 2003 ; Vol. 40, No. 4. pp. 382-94.
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Loukopoulos, P, Mungall, BA, Straw, RC, Thornton , JR & Robinson, WF 2003, 'Matrix metalloproteinase-2 and -9 involvement in canine tumors', Veterinary Pathology, vol. 40, no. 4, 12824510, pp. 382-94.

Matrix metalloproteinase-2 and -9 involvement in canine tumors. / Loukopoulos, Panayiotis; Mungall, Bruce A.; Straw, Rodney C.; Thornton , John R.; Robinson, Wayne F.

In: Veterinary Pathology, Vol. 40, No. 4, 12824510, 2003, p. 382-94.

Research output: Contribution to journalArticle

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Loukopoulos P, Mungall BA, Straw RC, Thornton JR, Robinson WF. Matrix metalloproteinase-2 and -9 involvement in canine tumors. Veterinary Pathology. 2003;40(4):382-94. 12824510.