HFE genotype affects exosome phenotype in cancer

Oliver D. Mrowczynski, A. B. Madhankumar, Becky Slagle-Webb, Sang Y. Lee, Brad E. Zacharia, James R. Connor

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 also shown to transfer this cargo to recipient cells and cause an increased oncogenic functionality in those recipient cells.

Original languageEnglish (US)
Pages (from-to)1921-1928
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Volume1861
Issue number8
DOIs
StatePublished - Aug 2017

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Exosomes
Tumors
Genotype
Phenotype
Neoplasms
Neuroblastoma
Polymorphism
Tumor Microenvironment
Hemochromatosis
Genes
Therapeutics
Tumor Burden
Monitoring
Recurrence
Proteins
Survival
Population

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Mrowczynski, Oliver D. ; Madhankumar, A. B. ; Slagle-Webb, Becky ; Lee, Sang Y. ; Zacharia, Brad E. ; Connor, James R. / HFE genotype affects exosome phenotype in cancer. In: Biochimica et Biophysica Acta - General Subjects. 2017 ; Vol. 1861, No. 8. pp. 1921-1928.
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HFE genotype affects exosome phenotype in cancer. / Mrowczynski, Oliver D.; Madhankumar, A. B.; Slagle-Webb, Becky; Lee, Sang Y.; Zacharia, Brad E.; Connor, James R.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1861, No. 8, 08.2017, p. 1921-1928.

Research output: Contribution to journalArticle

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