Extracellular pH is one of the main factors, which affects molecular processes involved in cell cycle, cell proliferation, differentiation, metabolism, protein synthesis, and motility of cells.
Due to the different processes that take place in the tumor tissue, the pH of the extracellular tumor environment is lower than the pH value of the extracellular environment of healthy tissue.
For a comprehensive understanding of the impact of acidic medium on cells we need to understand molecular processes that are cell response to the changes of extracellular pH and it is also necessary to understand the processes that cause acidification of the extracellular environment. Good understanding of processes is crucial in planning treatment of cancer, where it is necessary to take into account all the factors that have a significant impact on the level of effectiveness of medicines.
In this thesis, we have studied howtumor cells behave during electroporation in media with a lower pH value. For a better understanding of the impact of the acidic medium on electroporation of tumor cells we first investigated how acidic medium affects the cells, special attention was put on integrins. Integrins are adhesion protein receptors that transmit signals through the plasma membrane and induce the binding of ligands thereby forcing signal transmission through the cytoskeleton. They enable regulation of cytoskeletal organization, regulation of cell motility and have the ability to change paths of intracellular signals (angiogenesis, cell shape, proliferation, cell survival). Studies have shown that the acidic extracellular pH has an important influence on the activation of integrins.
Comparison of results of electroporation in natural medium and electroporation in acidic medium shows that the percentage of surviving cells in an acidic medium (pH = 6.7) is higher than in normal medium (pH = 7.84).
|
