HFE genotype affects exosome phenotype in cancer

Biochimica Et Biophysica Acta. General Subjects
Oliver D MrowczynskiJames R Connor

Abstract

Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored. We interrogated exosomes from human neuroblastoma cells that express wild-type or mutant forms of the HFE gene. HFE, one of the most common autosomal recessive polymorphisms in the Caucasian population, originally associated with hemochromatosis, has also been associated with increased tumor burden, therapeutic resistance boost, and negative impact on patient survival. Herein, we demonstrate that changes in genotype cause major differences in the molecular and functional properties of exosomes; specifically, HFE mutant derived exosomes have increased expression of proteins relating to invasion, angiogenesis, and cancer therapeutic resistance. HFE mutant derived exosomes were ...Continue Reading

Citations

Dec 5, 2019·Biomaterials Science·S BusattoP Bergese
Dec 20, 2019·PloS One·Sang Y LeeJames R Connor
Nov 16, 2018·Pharmaceuticals·Brian Chiou, James R Connor
Jun 1, 2018·BioMed Research International·Yan-Zi SunShao-Ming Wang

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