Features of matrix metalloproteinase-2 expression in the nuclei of tumor cells of a skin melanoma

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Abstract


Goal of the study. To compare expression of matrix metalloproteinase-2 (MMP-2) in the nuclei and cytoplasm of tumor cells and assess the mutual relation between the localization of MMP-2 expression and different clinical and morphologic criteria in patients with a skin melanoma. Materials and methods. Tumor samples obtained from paraffin blocks taken from patients suffering from a skin melanoma and treated at the Krasnoyarsk Territorial Oncologic Dispensary served as the object of the study. Skin tissue samples taken from patients suffering from a skin melanoma (n = 44) were obtained from the Krasnoyarsk Territorial Pathological Anatomy Bureau. Immunohistochemistry was performed based on a standard technique using primary anti-matrix metalloproteinase-2 antibodies. Results. MMP-2 expression was revealed in the nuclei of tumor cells of a skin melanoma in 43.1% of cases and in the cytoplasm in 56.9% of cases. No significant differences in MMP-2 expression in the nuclei and cytoplasm were revealed (p = 0.33). Patients with nuclear expression in tumor cells are characterized by a more favorable prognosis than patients with cytoplasmic enzyme expression in tumor complexes. No dependence of the intracellular localization of MMP-2 expression on the patient sex or age, tumor localization, Clark level of invasion, Breslow’s thickness, particular features of tumor lymphocyte infiltration, tumor growth phase, histological subtype, pigmentation, tumor ulceration and tumor stage according to AJCC (American Joint Committee on Cancer) was revealed. Conclusion. MMP-2 located in the nuclei can be related to hypoxia in the tumor tissue as well as increased peroxynitrite level, which, in its turn, can have an effect on the function and regulation of matrix metalloproteinases. Moreover, MMP-2 with an atypical localization can be related to tumor cells with different biological characteristics within the same tumor, which characterize the intratumoral heterogeneity of neoplasms. The biological and clinical role of changes in the intracellular localization of the enzyme needs further explanation.

M. B. Aksenenko

Krasnoyarsk State Medical University

Author for correspondence.
Email: aksenenko_mariya@mail.ru

Russian Federation

T. G. Ruksha

Krasnoyarsk State Medical University

Email: noemail@neicon.ru

Russian Federation

  1. Pakozdi A., Amin M.A., Haas C.S. et al. Macrophage migration inhibitory factor: a mediator of matrix metalloproteinase-2 production in rheumatoid arthritis. Arthritis Res Ther 2006; 8 (4): 1-14
  2. Smirnova O.V., Vyhristenko L.R. Role of cells of system of immunity in patogeneses bronchial asthma. Medicinskie novosti 2011; 5: 18-19
  3. MacNaul K.L, Chartrain N., Lark M.T., Hutchinson. N.I. Discoordinate expression of stromelysin collagenase, and tissue inhibitor of metalloproteinases-1 in rheumatoid human synovial fibroblasts. J Biol Chem 1990; 265: 17238-17245
  4. Leslie M.C., Bar-Eli M. Regulation of gene expression in melanoma: new approaches for treatment. J Cell Biochem 2005; 94: 25-38
  5. Kanomata N., Nakahara R., Oda T. et al. Expression and localization of mRNAs for matrix metalloproteinases and their inhibitors in mixed bronchioloalveolar carcinomas with invasive components Mod Pathol 2005; 18 (6): 828-837
  6. Delektorskaia V.V., Smirnova E.A., Ponomareva M.V. et al. Expression of matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in papillary thyroid cancer: an association with the clinical, morphological and ultra structural characteristics of a tumor. Arkhiv Patologii 2010; 72. (4): 3-6
  7. Branca M., Ciotti M., Giorgi C. Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are prognostic factors in cervical cancer, related to invasive disease but not to high-risk human papillomavirus (HPV) or virus persistence after treatment of CIN. Anticancer Res 2006; 26: 1543-1556.
  8. Kwan J.A., Schulze C.J., Wang W. et al.: Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiaomyocytes and is capable of cleaving poly (ADP-ribose) poly-merase (PARP) in vitro. FASEB J 2004, 18: 690-692.
  9. Baker A.H., Edwards D.R., Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci 2002; 115: 3719-3727.
  10. Schmalfeldt B., Prechtel D., Harting K. et al. Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. Clin Cancer Res 2001; 7: 2396-2404.
  11. McClelland R.A., Wilson D., Leake R. A multicentre study into the reliability of steroid receptor immunocytochemical assay quantification II Eur J Cancer 1991; 27: 711-715.
  12. Aldonyte R., Brantly M., Block E. et al. Nuclear localization of active matrix metalloproteinase-2 in cigarette smoke-exposed apoptotic endothelial cells. Exp Lung Res 2009; 35: 59-75.
  13. Amantea D., Corasaniti M.T., Mercuri N.B. et al. Brain regional and cellular localization of gelatinase activity in rat that have undergone transient middle cerebral artery occlusion. Neuroscience 2008; 152: 8-17.
  14. YangY., Candelario-Jalil E., Thompson J.F. et al. Increased intranuclear matrix metalloproteinase activity in neurons interferes with oxidative DNA repair in focal cerebral ischemia. J Neurochem 2010; 112: 134-149.
  15. Monvoisin A., Bisson C., Si-Tayeb K. et al. Involvement of matrix metalloproteinase type-3 in hepatocyte growth factor-induced invasion of human hepatocellular carcinoma cells. Int J Cancer 2002; 97: 157-162.
  16. Rebrova O. Ju. Statistical analysis of medical data. Moskva: MediaSfera 2002; 312 [Реброва О.Ю. Статистический анализ медицинских данных. М: МедиаСфера 2002; 312.]
  17. Kohrmann A. kammerer U.; Kapp M. et al. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. BMC Cancer 2009; 9: 188.
  18. Goroshinskaya I.A., Surikova E.I., Airapetov K.G. et al. Concentration of nitric oxide derivatives in blood of cancer patients with cerebral metastases and with different grade of endogenous intoxication. Siber J Oncol. 2009; 6 (36): 44-47.
  19. Bachmann I. M., Ladstein R. G., Straume О. et al. Tumor necrosis is associated with increased alphavbeta3 integrin expression and poor prognosis in nodular cutaneous melanomas. BMC Cancer 2008; 8: 362: 1-10.
  20. Gerashhenko T.S., Denisov E.V., Litvjakov N.V. et al. Intratumor heterogeneity: nature and biological significance. Biochemistry 2013; 78 (11): 1531-1549.
  21. Mannello F., Medda V. Nuclear localization of matrix metalloproteinases. Prog Histochem Cytochem 2012, 47: 27-58.

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