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An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles.
Ortiz, Angelica; Gui, Jun; Zahedi, Farima; Yu, Pengfei; Cho, Christina; Bhattacharya, Sabyasachi; Carbone, Christopher J; Yu, Qiujing; Katlinski, Kanstantsin V; Katlinskaya, Yuliya V; Handa, Simran; Haas, Victor; Volk, Susan W; Brice, Angela K; Wals, Kim; Matheson, Nicholas J; Antrobus, Robin; Ludwig, Sonja; Whiteside, Theresa L; Sander, Cindy; Tarhini, Ahmad A; Kirkwood, John M; Lehner, Paul J; Guo, Wei; Rui, Hallgeir; Minn, Andy J; Koumenis, Constantinos; Diehl, J Alan; Fuchs, Serge Y.
Afiliação
  • Ortiz A; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Gui J; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Zahedi F; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Yu P; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Cho C; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Bhattacharya S; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Carbone CJ; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Yu Q; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Katlinski KV; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Katlinskaya YV; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Handa S; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Haas V; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Volk SW; Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Brice AK; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Wals K; Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
  • Matheson NJ; Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
  • Antrobus R; Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
  • Ludwig S; Departments of Pathology, Immunology, and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Otorhinolaryngology, University of Duisburg-Essen, Duisburg, Germany.
  • Whiteside TL; Departments of Pathology, Immunology, and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  • Sander C; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  • Tarhini AA; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  • Kirkwood JM; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  • Lehner PJ; Department of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
  • Guo W; Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Rui H; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • Minn AJ; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Koumenis C; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Diehl JA; Department of Biochemistry, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Fuchs SY; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: syfuchs@upenn.edu.
Cancer Cell ; 35(1): 33-45.e6, 2019 01 14.
Article em En | MEDLINE | ID: mdl-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 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esteroide Hidroxilases / Receptor de Interferon alfa e beta / Vesículas Extracelulares / Neoplasias Pulmonares / Melanoma Limite: Animals / Humans Idioma: En Revista: Cancer Cell Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esteroide Hidroxilases / Receptor de Interferon alfa e beta / Vesículas Extracelulares / Neoplasias Pulmonares / Melanoma Limite: Animals / Humans Idioma: En Revista: Cancer Cell Ano de publicação: 2019 Tipo de documento: Article