ИСТИНА

Introduction The development of novel strategies for the inhibition of glioblastoma cells invasion depends crucially on our understanding of the characteristics of the interaction between tumor cells and cells of the tumor microenvironment. In the current study, the system of co- cultivation of human mesenchymal stem cells (MSCs) and glioblastoma cells was employed to explore the properties of the motility of cancer cells interacting with normal cells. Material and Methods U251 human glioblastoma cells and FetMSC mesenchymal stem cells derived from bone marrow of 5–6 week human embryos were used in the studies. Extracellular vesicles (EVs) and conditioned medium (CM) obtained from FetMSCs were added to glioblastoma cells, and vice versa, FetMSCs were treated with EVs and CM obtained from U251 cells. Additionally, U251 and FetMSC were directly co-cultivated with each other. These three types of experimental setups were carried out for 24 hours, while the cell motility was recorded using the CellVoyager CQ1 Benchtop High-Content Analysis System (Yokogawa). Results and Discussions The results obtained indicate that EVs from FetMSC caused an increase in the speed of U251 cells migration. The speed increased even more under the influence of CM derived from FetMSC, and was further increased in U251 cells when the latter were co-cultured with FetMSC. For FetMSC cells, the opposite effect was observed - under the influence of EVs derived from U251, stem cells reduced the speed of movement, that was further reduced when FetMSC were co-cultured with U251 cells. In addition to speed, we also studied the sinuosity of cell movement tracks. The tortuosity of U251 did not change, while sinuosity of FetMSC significantly increased both under the influence of EVs obtained from U251 and during co- cultivation with tumor cells. Conclusion Human MSCs are suppressed in motility while U251 glioblastoma cells' motility is increased when the two cells are co-cultured. The acquired results imply that the secretome produced by MSCs has the ability to accelerate the invasion of cancer cells, while intercellular contacts also play an important role and can be used in conjunction with the secretome's action. Cancer cells actively reorganizing the tumor microenvironment can reduce MSC motility.