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Investigation of matrix metalloproteinases and their tissue inhibitors in patients with cancer and benign diseases of endometrium. Part 2. Role matrix metalloproteinases in cancer and benign tumours of endometrium

DOI 10.18127/j20700997-201804-01


N.E. Kushlinskii - Corresponding-Member of RAS, Dr.Sc. (Med), Professor, Heard of the Department of Clinical Biochemistry and Laboratory Diagnostics, I.A. Evdokimov Moscow University of Medicine and Dentistry of Ministry of Health of the Russian Federation (Moscow)
S.V. Mushtenko - Post-graduate Student, Department of Oncology, I.A. Evdokimov Moscow University of Medicine and Dentistry of Ministry of Health of the Russian Federation (Moscow)
I.V. Tereshkina - Ph.D. (Med.), I.A. Evdokimov Moscow University of Medicine and Dentistry of Ministry of Health of the Russian Federation (Moscow)
V.D. Ermilova - Ph.D. (Med.), Department of Pathological Anatomy of Human Tumors, N.N. Blokhin National Medical Research Center of Oncology of Ministry of Health of the Russian Federation (Moscow)
E.S. Gershtein - Dr.Sc. (Biol.), Professor, Clinical Biochemistry Laboratory, N.N. Blokhin National Medical Research Center of Oncology of Ministry of Health of the Russian Federation (Moscow)
N.E. Levchenko - Dr.Sc. (Med.), Professor, Head of Oncogynecology Department, N.N. Blokhin National Medical Research Center of Oncology of Ministry of Health of the Russian Federation (Moscow)

The subject of this part of the review is a comparative analysis of up to date clinical studies of various classes of matrix metallopropteinases (MMPs: gelatinases – MMP-2 and 9; matrilysins – MMP-7 and 26) and tissue inhibitors of MMPs (TIMPs) in normal endometrium and its various non-oncologic and oncologic pathologies; evaluation of the associations between MMPs and TIMPs tissue expression or serum (plasma) levels with the main clinical and pathologic characteristics of endometrial carcinomas: tumor histologic type and differentiation grade, depth of endometrium invasion, frequency and levels of steroid hormones (estrogen and progesterone) receptors expression, disease prevalence and prognosis. The role of MMPs in the pathogenesis of oncologic and non-oncologic diseases of endometrium make them attractive and potent targets for pharmacotherapy starting from low-molecular inhibitors interacting with MMPs’ active sites and including macromolecular inhibitors affecting MMPs exosites, allosteric inhibitors, medications based on endogeneous inhibitors, antibodies, etc. Several approaches to anti-MMPs  therapy were developed in experimental studies: 1) blockade of MMPs synthesis, 2) suppression of MMPs interaction with molecules directing them to cellular surface and intercellular space, 3) inhibition of MMPs’ enzymatic activity. Meanwhile, the involvement of MMPs in multitude molecular pathways, broad and frequently overlapping substrate specificity, expression in the majority of tissues, high level of homology between different MMPs, as well as adverse toxic effects impede the development of corresponding targeted drugs and their implication in clinical practice. The published by the present time data on the clinical significance of MMPs and TIMPs in endometrial cancer are not numerous and in major part are controversial. The analysis of these publication allow to suggest that the most perspective tissue marker of endometrial cancer prognosis should be MMP-2 whose expression level increases with malignancy grade and indices of disease advancement, and according to the results of several independent studies affects the overall and relapse-free survival of the patients. As far as the clinical value of MMPs and TIMPs circulating in the peripheral blood, the studies in this field are still at the beginning and require further development.

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