Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press4210.17650/2313-805X.2015.2.3.21-29REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИTHE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORSМЕХАНИЗМЫ ПРОТОНИРОВАНИЯ МЕЖКЛЕТОЧНОГО ПРОСТРАНСТВА В ОПУХОЛЯХKoblyakovV. A.КобляковВ. А.
Russian Federation

Кобляков Валерий Александрович

kobliakov@rambler.ruResearch Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia , MoscowНаучно-исследовательский институт канцерогенеза ФГБУ «Российский онкологический научный центр имени Н.Н. Блохина» Минздрава России, Москва150920152321291812201518122015Copyright ©; 2015, Koblyakov V.A.Copyright ©; 2015, Кобляков В.А.2015Koblyakov V.A.Кобляков В.А.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/42

One of the differences between normal and tumor cells is more intensive acidification of the extracellular area in tumor cells compare with intracellular area. Low pH in extracellular region stimulates invasion and metastatic process. This effect of low pH is not fully understood. There are some mechanisms of maintenance of low pH in extracellular region of tumor. In tumor some cells exist in hypoxic state. It is accepted that invasion and metastatic process occur at hypoxic area of tumor. During hypoxia due to activation of transcription factor HIF-1α the tumor cells turn to glycolysis and the end point of glucose oxidation is lactate. The formation of lactate from pyruvate is catalyzed by HIF-1α-dependent lactate dehydrogenase isoform. Accumulation lactate with pK 3.9 is dangerous for cells and monocarboxilate transporters which transport lactate and proton from cytosol are activated. The other mechanism of extracellular protonation is realized by functioning of HIF-1α-dependent carbonic anhydrase (СА IX). СА IX catalyzed the proton formation by interaction of carbonate dioxide with water. СА IX is situated in cell membrane in such manner, that active centre is directed in extracellular matrix. The function of other transmembrane proton pomp is not associated with hypoxia. The activation of Na+/H+ exchanger occur by stress, like osmotic chock or proliferation stimuli. In would be reviewed here the mechanisms of activation of proton pumps. It is shown the results of experiments devoted the effects of different types of inhibitors on tumor growth in cell culture and in vivo. It is suggest that proton pump inhibitors could be in complex with “classical” antineoplastic compounds perspective in cancer treatment.

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