20.500.12556/DiRROS-19706 Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell lines Glioblastoma multiforme are an aggressive form of brain tumors that are characterized by distinct invasion of single glioblastoma cells, which infiltrate the brain parenchyma. This appears to be stimulated by the communication between cancer and stromal cells. Mesenchymal stem cells (MSCs) are part of the glioblastoma microenvironment, and their ‘cross-talk’ with glioblastoma cells is still poorly understood. Here, we examined the effects of bone marrow-derived MSCs on two different established glioblastoma cell lines U87 and U373. We focused on mutual effects of direct MSC/glioblastoma contact on cellular invasion in three-dimensional invasion assays in vitro and in a zebrafish embryo model in vivo. This is the first demonstration of glioblastoma cell-type-specific responses to MSCs in direct glioblastoma co-cultures, where MSCs inhibited the invasion of U87 cells and enhanced the invasion of U373. Inversely, direct cross-talk between MSCs and both of glioblastoma cell lines enhanced MSC motility. MSC-enhanced invasion of U373 cells was assisted by overexpression of proteases cathepsin B, calpain1, uPA/uPAR, MMP-2, -9 and -14, and increased activities of some of these proteases, as determined by the effects of their selective inhibitors on invasion. In contrast, these proteases had no effect on U87 cell invasion under MSC co-culturing. Finally, we identified differentially expressed genes, in U87 and U373 cells that could explain different response of these cell lines to MSCs. In conclusion, we demonstrated that MSC/glioblastoma cross-talk is different in the two glioblastoma cell phenotypes, which contributes to tumor heterogeneity. glioblastoma multiforme proteases mesenchymal stem cells tumor heterogeneity zebrafish model true false true Angleški jezik Ni določen Neznano 2024-07-24 03:46:21 2024-07-24 15:11:45 2024-07-25 04:14:56 0000-00-00 00:00:00 2017 0 0 Nasl. z nasl. zaslona; Opis vira z dne 13. 2. 2017; str. 25482-25499 no. 15 Vol. 8 2017 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2017-03-09 577.2 1949-2553 10.18632/oncotarget.16041 4238415 RAZ_Breznik_Barbara_2017.pdf RAZ_Breznik_Barbara_2017.pdf 1 15A63F2D8D3B1C20349EFEB03EFEED26 fc87d74a827dc2da3e65068ffd21a61d3b547fe0c6b20c76faa6780b0d7bf250 24460231-49ae-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27379 https://doi.org/10.18632/oncotarget.16041 0 3bb640e4-49ae-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27380 Nacionalni inštitut za biologijo 0 0 0