20.500.12556/DiRROS-6103 Heterogeneous glioblastoma cell cross-talk promotes phenotype alterations and enhanced drug resistance Glioblastoma multiforme is the most lethal of brain cancer, and it comprises a heterogeneous mixture of functionally distinct cancer cells that affect tumor progression. We examined the U87, U251, and U373 malignant cell lines as in vitro models to determine the impact of cellular cross-talk on their phenotypic alterations in co-cultures. These cells were also studied at the transcriptome level, to define the mechanisms of their observed mutually affected genomic stability, proliferation, invasion and resistance to temozolomide. This is the first direct demonstration of the neural and mesenchymal molecular fingerprints of U87 and U373 cells, respectively. U87-cell conditioned medium lowered the genomic stability of U373 (U251) cells, without affecting cell proliferation. In contrast, upon exposure of U87 cells to U373 (U251) conditioned medium, U87 cells showed increased genomic stability, decreased proliferation rates and increased invasion, due to a plethora of produced cytokines identified in the co-culture media. This cross talk altered the expression 264 genes in U87 cells that are associated with proliferation, inflammation, migration, and adhesion, and 221 genes in U373 cells that are associated with apoptosis, the cell cycle, cell differentiation and migration. Indirect and direct co-culturing of U87 and U373 cells showed mutually opposite effects on temozolomide resistance. In conclusion, definition of transcriptional alterations of distinct glioblastoma cells upon co-culturing provides better understanding of the mechanisms of glioblastoma heterogeneity, which will provide the basis for more informed glioma treatment in the future. glioblastoma heterogeneity U87 cells temozolomide resistance cellular cross-talk transcriptomics true false true Angleški jezik Neznan jezik Delo ni kategorizirano 2016-06-09 03:18:39 2024-07-29 12:47:08 2024-07-30 04:00:44 0000-00-00 00:00:00 2015 0 0 str. 40998-41017 no. 38 Vol. 6 2015 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2015-10-20 1949-2553 577.2 10.18632/oncotarget.5701 3643471 3833969 http://dx.doi.org/10.18632/oncotarget.5701 1 https://dirros.openscience.si/Dokument.php?lang=slv&id=6221 RAZ_Koren_Ana_2015.pdf RAZ_Koren_Ana_2015.pdf 1 3E3120C5EA2632DEE8C8DF6233500623 38e4624b09425a3d17928b9215c95611dfcd8fff8bdd8aa5434939724ec3d9d5 0077f8c6-4d88-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27676 Nacionalni inštitut za biologijo 0 0 0