Vol 2, No 3 (2015)

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.

Syndecan-1 (CD138) is one of the main cell markers used in flow cytometric analysis of multiple myeloma (MM) cells. CD138 and several other markers – CD19, CD45, CD56 – which are often used in order to characterize MM and give the possibility to differentiate MM cells from the normal plasmocytes are described. Only CD138-expressing MM plasma cells are usually taken into account in MM analysis. The current literature data point out that CD138-negative MM plasma cells could be important for MM prognosis, as well. This cell population demonstrates certain properties that are typical to the cancer stem cells. CD138-negative cell population is characterized by higher proliferation, clonogenicity, engraftment in immunodeficient mice as compared to CD138 expressing plasma cells. Besides that, CD138-negative cells were more resistant than CD138-positive cells to the drugs that are used in MM chemotherapy. CD138-negative plasma cells are able to produce CD138 expressing cells upon a long-term culture in vitro and thus to reproduce the heterogenic in CD138 expression population of MM plasma cells. The results of these investigations, as well as statistical data indicating the worse overall survival of CD138 low expressing MM patients point out that CD138-negative population of MM plasma cells should be taken into consideration in MM analysis. Thus, it could be important to find the new markers distinguishing the plasma cell population differing in CD138 expression. Vascular endothelial growth factor receptor VEGFR3 was found to be a new marker with such properties.