THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORS
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 mec...
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ABV-press
2015-12-01
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| Series: | Успехи молекулярной онкологии |
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| Online Access: | https://umo.abvpress.ru/jour/article/view/42 |
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| author | V. A. Koblyakov |
| author_facet | V. A. Koblyakov |
| author_sort | V. A. Koblyakov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a110986acde54b9da54c3d69bd145565 |
| institution | Kabale University |
| issn | 2313-805X 2413-3787 |
| language | Russian |
| publishDate | 2015-12-01 |
| publisher | ABV-press |
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| series | Успехи молекулярной онкологии |
| spelling | doaj-art-a110986acde54b9da54c3d69bd1455652025-08-20T03:44:07ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872015-12-0123212910.17650/2313-805X.2015.2.3.21-2942THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORSV. A. Koblyakov0Research Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia , MoscowOne 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.https://umo.abvpress.ru/jour/article/view/42invasion and metastasis, lactate dehydrogenase, monocarboxilate transporter, carbonic anhydrase, na+/h+ exchanger, hypoxia, glycolysis, hif-1α |
| spellingShingle | V. A. Koblyakov THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORS Успехи молекулярной онкологии invasion and metastasis, lactate dehydrogenase, monocarboxilate transporter, carbonic anhydrase, na+/h+ exchanger, hypoxia, glycolysis, hif-1α |
| title | THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORS |
| title_full | THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORS |
| title_fullStr | THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORS |
| title_full_unstemmed | THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORS |
| title_short | THE MECHANISMS OF PROTONATION OF EXTRACELLULAR MATRIX IN TUMORS |
| title_sort | mechanisms of protonation of extracellular matrix in tumors |
| topic | invasion and metastasis, lactate dehydrogenase, monocarboxilate transporter, carbonic anhydrase, na+/h+ exchanger, hypoxia, glycolysis, hif-1α |
| url | https://umo.abvpress.ru/jour/article/view/42 |
| work_keys_str_mv | AT vakoblyakov themechanismsofprotonationofextracellularmatrixintumors AT vakoblyakov mechanismsofprotonationofextracellularmatrixintumors |