Journal article
An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
Cancer cell, Vol.35(1), pp.33-45.e6
01/14/2019
DOI: 10.1016/j.ccell.2018.12.001
PMCID: PMC6336114
PMID: 30645975
Abstract
Tumor-derived extracellular vesicles (TEV) "educate'' healthy cells to promote metastases. We found that melanoma TEV downregulated type I interferon (IFN) receptor and expression of IFN-inducible cholesterol 25-hydroxylase (CH25H). CH25H produces 25-hydroxycholesterol, which inhibited TEV uptake. Low CH25H levels in leukocytes from melanoma patients correlated with poor prognosis. Mice incapable of down-regulating the IFN receptor and Ch25h were resistant to TEV uptake, TEV-induced pre-metastatic niche, and melanoma lung metastases; however, ablation of Ch25h reversed these phenotypes. An anti-hypertensive drug, reserpine, suppressed TEV uptake and disrupted TEV-induced formation of the pre-metastatic niche and melanoma lung metastases. These results suggest the importance of CH25H in defense against education of normal cells by TEV and argue for the use of reserpine in adjuvant melanoma therapy.
Details
- Title: Subtitle
- An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
- Creators
- Angelica Ortiz - University of PennsylvaniaJun Gui - University of PennsylvaniaFarima Zahedi - University of PennsylvaniaPengfei Yu - University of PennsylvaniaChristina Cho - University of PennsylvaniaSabyasachi Bhattacharya - University of PennsylvaniaChristopher J. Carbone - University of PennsylvaniaQiujing Yu - University of PennsylvaniaKanstantsin Katlinski - University of PennsylvaniaYuliya Katlinskaya - University of PennsylvaniaSimran Handa - University of PennsylvaniaVictor Haas - University of PennsylvaniaSusan W. Volk - University of PennsylvaniaAngela K. Brice - University of PennsylvaniaKim Wals - National Institute for Health ResearchNicholas J. Matheson - National Institute for Health ResearchRobin Antrobus - National Institute for Health ResearchSonja Ludwig - University of Duisburg-EssenTheresa L. Whiteside - University of PittsburghCindy Sander - University of PittsburghAhmad A. Tarhini - University of PittsburghJohn M. Kirkwood - University of PittsburghPaul J. Lehner - National Institute for Health ResearchWei Guo - University of PennsylvaniaHallgeir Rui - Medical College of WisconsinAndy J. Minn - University of PennsylvaniaConstantinos Koumenis - University of PennsylvaniaJ. Alan Diehl - MUSC Hollings Cancer CenterSerge Y. Fuchs - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Cancer cell, Vol.35(1), pp.33-45.e6
- DOI
- 10.1016/j.ccell.2018.12.001
- PMID
- 30645975
- PMCID
- PMC6336114
- NLM abbreviation
- Cancer Cell
- ISSN
- 1535-6108
- eISSN
- 1878-3686
- Publisher
- Elsevier
- Number of pages
- 19
- Grant note
- PA Department of Health FY18 2017 Health Research Formula Fund Merial Veterinary Scholars Program Fellowship PO1 CA165997 / NIH/NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CSF MR/P008801/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) WPA15-02 / NHSBT Undergraduate Student Scholars Program in the Center for Molecular Studies in Digestive and Liver Disease, University of Pennsylvania MR/P008801/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) CA092900; CA216936; CA188575 / R01 grants Pittsburgh-Essen-Partnership Program PRF 101835/Z/13/Z / Wellcome Trust
- Language
- English
- Date published
- 01/14/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984949512402771
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