AI Article Synopsis

  • Glioblastoma multiforme is a highly deadly brain cancer with diverse cell types that influence tumor growth, and researchers studied specific cell lines (U87, U251, U373) to understand how they interact in co-cultures.
  • These interactions were analyzed at the transcriptional level to investigate their effects on genomic stability, cell growth, invasion, and resistance to the cancer drug temozolomide.
  • The study found that the cellular cross-talk notably altered gene expression related to various cancer processes, revealing important insights into glioblastoma's complexity and potential treatment strategies.

Article Abstract

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747385PMC
http://dx.doi.org/10.18632/oncotarget.5701DOI Listing

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