Document Type : Original Article

Authors

Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

Abstract

Recently, matrix metalloproteinases (MMP), in particular the gelatinases MMP-2 and MMP-9, generally considered as tumor markers for clinical applications. A longitudinal 2-years follow-up survey was performed on dogs with cutaneous tumor. Serum samples were obtained from 22 dogs with different cutaneous tumors and 22 health dogs at the time of surgery and one month, three months and one year after surgery. Gelatin zymography, hematological and biochemical assessment were performed for all serum samples. The serum alkaline phosphatase activity in dogs with malignant tumors was significantly higher than that in dogs with benign tumors and control cases. Latent forms of MMP-2 and MMP-9 were detected in all of the tumor cases. Gelatin zymography showed active form of MMP-9 in 12 cases (three benign and nine malignant tumors) and active form of MMP-2 in one fibrosarcoma case. Serum activity of active-MMP-9 and total MMP-9 was significantly higher in dogs with cutaneous tumors than those in controls. Tumor cases had higher serum activity of active-MMP-9 rather than controls. MMPs and alkaline phosphatase activities in serum were decreased significantly after surgery. Only one case with perianal gland adenoma showed recurrence of tumor four months after surgery in which active form of MMP-9 had identified one month before recurrence. According to the findings, it will be useful to measure ALP, MMP-2 and MMP-9 activities in the serum of dogs with cutaneous tumor for determination of tumor behavior before surgical treatment.

Keywords

Main Subjects

  1.  

    1. Björklund M, Koivunen E. Gelatinase-mediated migration and invasion of cancer cells. Biochim Biophys Acta (BBA)-Reviews on Cancer. 2005; 1755(1):37-69.
    2. Foda HD, Zucker S. Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis. Drug Discov Today 2001; 6(9):478-482.
    3. Turpeenniemi-Hujanen T. Gelatinases (MMP-2 and-9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie 2005; 87(3):287-297.
    4. Miya K, Misumi K, Miyoshi N, et al. Interpreting gelatinase activity in tumor tissue and serum as a prognostic marker of naturally developing canine tumors. J Vet Med Sci. 2005; 67(8):769-775.
    5. Yaman E, Yalcin B, Utkan G, et al. Prognostic significance of serum matrix metalloproteinase 9 (MMP-9) levels in patients with sarcomas. UHOD-Uluslar Hematol J 2008; 18(2):79-84.
    6. La Rocca G, Pucci-Minafra I, Marrazzo AN, Taormina P, Minafra S. Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera. Brit J Cancer 2004; 90(7):1414-1421.
    7. Laack E, Köhler A, Kugler C, et al. Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer. Ann Oncol 2002; 13(10):1550-1557.
    8. Gentilini F, Calzolari C, Turba ME, et al. Prognostic value of serum vascular endothelial growth factor (VEGF) and plasma activity of matrix metalloproteinase (MMP) 2 and 9 in lymphoma-affected dogs. Leukemia Res 2005; 29(11):1263-1269.
    9. Aresu L, Giantin M, Morello E, et al. Matrix metalloproteinases and their inhibitors in canine mammary tumors. BMC Vet Res 2011; 7(1):33.
    10. Klein G, Vellenga E, Fraaije MW, et al. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol 2004:50(2): 87-100.
    11. Loukopoulos P, Mungall BA, Straw RC, Thornton JR, Robinson WF. Matrix metalloproteinase-2 and-9 involvement in canine tumors. Vet Pathol Online 2003; 40(4):382-394.
    12. Giantin M, Aresu L, Benali S, et al. Expression of matrix metalloproteinases, tissue inhibitors of metallo-proteinases and vascular endothelial growth factor in canine mast cell tumors. J Comp Pathol 2012; 147(4):419-429.
    13. Leibman NF, Lana SE, Hansen RA, et al. Identification of matrix metalloproteinases in canine cutaneous mast cell tumors. J Vet Intern Med 2000; 14(6):583-586.
    14. Bastianello SS. A survey on neoplasia in domestic species over a 40-year period from 1935 to 1974 in the Republic of South Africa. Tumours occurring in dogs: Onderstepoort J Vet Res 1983; 50(3):199-220.
    15. Cotchin E. Further observations on neoplasms in dogs, with particular reference to site of origin and malignancy. Brit Vet J 1954; 110:218-230.
    16. Morris, J. and Dobson, J. Small animal oncology. New York, USA; John Wiley & Sons 2008; 50-77.
    17. Mukaratirwa S, Chipunza J, Chitanga S, et al. Canine cutaneous neoplasms: Prevalence and influence of age, sex and site on the presence and potential malignancy of cutaneous neoplasms in dogs from Zimbabwe. J S Afr Vet Assoc 2005;76(2):59-62.
    18. Pakhrin B, Kang MS, Bae IH, et al. Retrospective study of canine cutaneous tumours in Korea. J Vet Sci 2007;8(3):229-236.
    19. Vail DM, Withrow SJ. Tumors of the skin and subcutaneous tissues. Small animal clinical oncology. 4th ed. St. Louis, USA; Saunders 2007; 375-401.
    20. Weiss E, Frese K. Tumours of the skin. Bull World Health Organ 1974;50(1-2):79-100.
    21. Jubb K. Palmer’s pathology of domestic animals. St. Louis, USA; Saunders 2007; 553-781.
    22. Meuten DJ, editor. Tumors in domestic animals. New York, USA; John Wiley & Sons 2008; 45-118.
    23. Coughlan AR, Robertson DH, Burke R, et al. Isolation and identification of canine matrixmetalloproteinase-2 (MMP-2). Vet J 1998; 155(3):231-237.
    24. Karayannopoulou, M, Koutinas, AF, Polizopoulou, ZS, et al. Total serum alkaline phosphatase activity in dogs with mammary neoplasms: A prospective study on 79 natural cases. J Vet Med A Physiol Pathol Clin Med 2003;50(10): 501-505.
    25. Hamilton JM, Wright J, Kight D. Alkaline phosphatase levels in canine mammary neoplasia. Vet Rec 1973; 93(5): 121-123.
    26. Huggins C. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941; 1: 293-307.