Tmic-11. hfe genotype alters exosome profiles in cancer

Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. A major focus in cancer biology is the impact of exosomes on metastasis and the microenvironment. The major goal of this study was to determine if changes in HFE genotype, associated with aggressive cancer phenotype, have significant effects on exosome profile. HFE, the most common autosomal recessive polymorphism in the Caucasian population, originally associated with hemochromatosis, is also associated with increased tumor burden, therapeutic resistance boost, and negative impact on survival. We used immunoblots to analyze protein expression differences between exosomes. We also used functional assays, such as invasion and angiogenesis assays, to determine functional changes caused by HFE mutant cell derived exosomes. We demonstrate that HFE mutant derived exosomes have increased expression of proteins relating to the ferrome, invasion, angiogenesis, and cancer therapeutic resistance. These exosomes can induce altered functionality such as increased angiogenesis, migration, invasion and resistance to radiation in wild-type HFE cells. These novel findings are the first to demonstrate genotype influence on exosomes and that the exosomes from a cell line carrying a mutation can alter the phenotype in a wild-type cell line. Moreover, the exosomes from the mutant cell line transfer the more aggressive and treatment resistant phenotype t...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research