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Vol 55(2021) N 6 p. 910-918; DOI 10.1134/S0026893321050095 Full Text

N.A. Mitkin1*, A.S. Ustiugova1, A.N. Uvarova1, K.A. Rumyantsev2, K.V. Korneev1, V.V. Pavshintsev3

Serum of Mice Immunized with Mt1-MMP Metalloproteinase Reduces Migration Potential of Pancreatic Cancer Cells

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Moscow Clinical Scientific Center, Moscow, 111123 Russia
3Institute of Mitoengineering MSU, Moscow, 119192 Russia

*mitkin.n.a@gmail.com
Received - 2021-03-18; Revised - 2021-05-05; Accepted - 2021-05-13

Expression levels of matrix metalloproteinases, in particular MT1-MMP, are elevated in pancreatic cancer (PC) cells, and this is associated with increased tumor proliferation, invasion, and migration. MT1-MMP is considered a promising target for drug therapy of PC, but the use of inhibitors and therapeutic antibodies to MT1-MMP is limited because maximal efficiency is only observed in a narrow time interval, at the early asymptomatic stages of the disease. This problem could be solved by immunization to MPs at the moment of detection of the primary tumor. This therapeutic effect could be provided by specific antibodies that can be re-produced in case of relapses. Here, we selected the optimal mode for immunization of mice with MT1-MMP fragments that allows us to obtain a high titer of specific antibodies in the blood serum. The obtained antiserums effectively inhibited MT1-MMP enzymatic activity, migration of PANC-02 PC cells through the collagen matrix, and activation of the main inducers of epithelial -mesenchymal transition, TGF-β and MMP-2. These results maybe useful in the development of drugs for PC treatment, and the approach we propose might form the basis for design of antitumor drugs with prolonged action.

matrix metalloproteinases, MT1-MMP, peptides, immunization, anti-serum, pancreatic cancer, TGF-β, epithelial-mesenchymal transition, mice, PANC-02



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