ArticleCancer cell2019
An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles.
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Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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103citing papers in PubMed
8.2field-weighted citation impact, top 2% of its field
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Who cites it
103 citing papers in PubMed, 151 citations in OpenAlex.
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Antihypertensive Drugs as Potential Repositioning Options for Melanoma: A Map of Pre-Clinical Evidence.Diseases (Basel, Switzerland) · 2026Review
- Switching tumor-derived extracellular vesicles off and on via targeted proteolysis to shift toward immunogenic phenotypes.Signal transduction and targeted therapy · 2026Article
- Machine learning-guided multimodal profiling defines perturbed immune states at the time of cancer diagnosis.Briefings in bioinformatics · 2026Article
- Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.Clinical & experimental metastasis · 2026Review
- The Phospholipid Bis(monoacylglycero)Phosphate Confers Antitumour Immunogenicity to Exosomes Secreted by Dendrogenin A, Which Activates Its Biosynthesis in Tumour Cells.Journal of extracellular vesicles · 2026Article
- Mechanisms of tumor-derived extracellular vesicle-mediated immunometabolic reprogramming and immunotherapeutic resistance.Molecular cancer · 2026Review
- Silencing of Cholesterol 25-Hydroxylase Attenuates Lipopolysaccharide-Induced Cardiomyocyte Damage In Vitro.Journal of cellular and molecular medicine · 2025Article
- Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity.Cancer cell · 2025Article
- Review
- Exploring molecular and cellular mechanisms of Pre-Metastatic niche in renal cell carcinoma.Molecular cancer · 2025Review
- Lymphatic-derived oxysterols promote anti-tumor immunity and response to immunotherapy in melanoma.Nature communications · 2025Article
- Sleepyhead, deadly awakening: the dynamics of metastatic organotropism, tumor dormancy and therapeutic implications.Frontiers in oncology · 2025Review
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Cholesterol: The driving force behind the remodeling of tumor microenvironment in colorectal cancer.Heliyon · 2024Review
- Extracellular vesicles in cancers: mechanisms, biomarkers, and therapeutic strategies.MedComm · 2024Review
- Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells.Nature reviews. Cancer · 2024Review
- Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies.Science translational medicine · 2024Article
- Inflammatory recruitment of healthy hematopoietic stem and progenitor cells in the acute myeloid leukemia niche.Leukemia · 2024Article
- A Single-Atom Manganese Nanozyme Mn-N/C Promotes Anti-Tumor Immune Response via Eliciting Type I Interferon Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 6 institutions in 3 countries.
Angelica OrtizDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jun GuiDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Farima ZahediDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pengfei YuDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christina ChoDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sabyasachi BhattacharyaDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher J CarboneDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Qiujing YuDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kanstantsin V KatlinskiDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yuliya V KatlinskayaDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Simran HandaDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Victor HaasDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Susan W VolkDepartment of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Angela K BriceDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kim WalsDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Nicholas J MathesonDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Robin AntrobusDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Sonja LudwigDepartments of Pathology, Immunology, and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Otorhinolaryngology, University of Duisburg-Essen, Duisburg, Germany.
Theresa L WhitesideDepartments of Pathology, Immunology, and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Cindy SanderDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Ahmad A TarhiniDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
John M KirkwoodDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Paul J LehnerDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Wei GuoDepartment of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hallgeir RuiDepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Andy J MinnDepartment of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Constantinos KoumenisDepartment of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Alan DiehlDepartment of Biochemistry, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Serge Y FuchsDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: syfuchs@upenn.edu.
University of Pennsylvania · USNational Institute for Health Research · GBUniversity of Pittsburgh · USMedical College of Wisconsin · USMedical University of South Carolina · USUniversity of Duisburg-Essen · DE
Funding
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MUPR, interferon signaling and tumorigenesisP01CA165997 · NCI · UNIVERSITY OF PENNSYLVANIA · PI FUCHS, SERGE Y · 2013 to 2023
$10.9MRole of HOS in Cell Transformation and ApoptosisR01CA092900 · NCI · UNIVERSITY OF PENNSYLVANIA · PI FUCHS, SERGE Y · 2001 to 2021
$5.3MTraining In Tumor VirologyT32CA115299 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2006 to 2021
$4.7MNegative regulation of myeloid-derived suppressive cells in cancerR01CA216936 · NCI · WISTAR INSTITUTE · PI FUCHS, SERGE Y, NEFEDOVA, YULIA · 2018 to 2022
$2.5MShort-term Training: students in health professional schoolsT35OD010919 · OD · UNIVERSITY OF PENNSYLVANIA · PI Michael Lee Atchison · 2012 to 2026
$1.8MProlactin pathways and metastatic progression of ER-positive breast cancerR01CA188575 · NCI · THOMAS JEFFERSON UNIVERSITY · PI RUI, HALLGEIR · 2015 to 2019
$1.8MIFNARI downregulation in melanoma cells and stromal cells promotes melanoma progression and pulmonary metastasisF32CA206431 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ORTIZ, ANGELICA · 2016 to 2017
$111kMedical Research Council MR/P008801/1NCI NIH HHS F32 CA206431NCI NIH HHS P01 CA165997NCI NIH HHS R01 CA092900NCI NIH HHS R01 CA188575NCI NIH HHS R01 CA216936NCI NIH HHS T32 CA009140NCI NIH HHS T32 CA115299NIH HHS T35 OD010919Wellcome Trust 101835/Z/13/ZWellcome Trust 210688/Z/18/Z
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.
Indexed as
AnimalsCell Line, TumorDisease ProgressionExtracellular VesiclesGene Expression Regulation, NeoplasticGene Knockout TechniquesHumansInterferonsLung NeoplasmsMelanomaMiceNeoplasm MetastasisOxysterolsReceptor, Interferon alpha-betaReserpineSteroid Hydroxylasescholesterol 25-hydroxylaseIFNAR2 protein, humanInterferonsOxysterolsReceptor, Interferon alpha-betaReserpineSteroid Hydroxylases25-hydroxycholesteroladjuvant therapyexosomesextracellular vesiclesIFNAR1interferonmelanomametastasispre-metastatic nichereserpine
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