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CpG on carbon nanotubes inhibits migration of brain tumor cells while activating immune cells

ABSTRACT: Even when treated with aggressive current therapies, patients with glioblastoma usually survive less than two years and exhibit a high rate of recurrence. CpG is an oligonucleotide that activates the innate immune system via TLR9 activation. Injection of CpG into glioblastoma tumors showed promise as an immunotherapy in mouse models but proved disappointing in human trials. One aspect of glioma that is not addressed by CpG therapy alone is the highly invasive nature of glioma cells, which is associated with resistance to radiation and chemotherapy. Here, we demonstrate that single-walled carbon nanotubes non-covalently functionalized with CpG (SWNT/CpG) not only retain the immunostimulatory property of the CpG, but interestingly also inhibit the migration of glioma cells without affecting cell viability or proliferation. SWNT/CpG activated macrophages by induction of the TLR9/NF-κB pathway, but actually decreased NF-κB activation in glioma cells. By using RNA-seq to compare the effect of SWNT/CpG treatment on glioma cells and macrophages, we confirmed that SWNT/CpG treatment has cell type-specific effects on gene expression. Through RNA-seq analysis, we identified a number of differentially affected pathways which may be involved in glioma cell migration inhibition and observed reduced gene expression in DNA repair pathways for SWNT/CpG-treated glioma cells. The migration inhibition of glioma cells was correlated with reduced intracellular levels of reactive oxygen species (ROS), suggesting that an antioxidant-based mechanism mediates the observed effects. To our knowledge, SWNT/CpG is the first therapy that inhibits the migration of cancer cells while stimulating the immune system.

ORGANISM(S): Mus musculus

PROVIDER: GSE102294 | GEO | 2018/02/06

REPOSITORIES: GEO

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