An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
| Autor: | Nicholas J Matheson, Susan W. Volk, Ahmad A. Tarhini, J. Alan Diehl, Jun Gui, Paul J. Lehner, Yuliya V. Katlinskaya, Angelica Ortiz, Constantinos Koumenis, Angela K Brice, John M. Kirkwood, Wei Guo, Hallgeir Rui, Christina Cho, Simran Handa, Sabyasachi Bhattacharya, Christopher J. Carbone, Pengfei Yu, Sonja Ludwig, Cindy Sander, Serge Y. Fuchs, Andy J. Minn, Robin Antrobus, Farima Zahedi, Qiujing Yu, Kim Wals, Theresa L. Whiteside, Victor Haas, Kanstantsin V. Katlinski |
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| Přispěvatelé: | Matheson, Nicholas [0000-0002-3318-1851], Lehner, Paul [0000-0001-9383-1054], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms Reserpine pre-metastatic niche Oxysterol THP-1 Cells 25-hydroxycholesterol Medizin exosomes Receptor Interferon alpha-beta Metastasis Extracellular Vesicles Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine Interferon Cell Line Tumor melanoma medicine Adjuvant therapy metastasis Animals Humans Neoplasm Metastasis Receptor IFNAR1 Chemistry Melanoma adjuvant therapy interferon Oxysterols Cell Biology medicine.disease Microvesicles Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Cell culture 030220 oncology & carcinogenesis Steroid Hydroxylases Disease Progression Cancer research Interferons medicine.drug |
| Zdroj: | Cancer Cell. 35:33-45.e6 |
| ISSN: | 1535-6108 |
| Popis: | 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 downregulating 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. |
| Databáze: | OpenAIRE |
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