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

Autor: Mitkin NA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.; mitkin.n.a@gmail.com., Ustiugova AS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia., Uvarova AN; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia., Rumyantsev KA; Moscow Clinical Scientific Center, Moscow, 111123 Russia., Korneev KV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia., Pavshintsev VV; Institute of Mitoengineering MSU, Moscow, 119192 Russia.
Jazyk: ruština
Zdroj: Molekuliarnaia biologiia [Mol Biol (Mosk)] 2021 Nov-Dec; Vol. 55 (6), pp. 1011-1020.
DOI: 10.31857/S0026898421060094
Abstrakt: 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.
Databáze: MEDLINE