دورية أكاديمية
أعرض في EDS

Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche.

التفاصيل البيبلوغرافية
العنوان: Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche.
المؤلفون: de Oliveira KG; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Bång-Rudenstam A; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Beyer S; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Boukredine A; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Talbot H; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Governa V; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Johansson MC; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Månsson AS; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Forsberg-Nilsson K; Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Division of Cancer and Stem Cells, University of Nottingham Biodiscovery Institute, Nottingham, UK., Bengzon J; Department of Clinical Sciences, Section of Neurosurgery, Lund University, Lund, Sweden., Malmström J; Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden., Welinder C; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden., Belting M; Department of Clinical Sciences, Lund, Section of Oncology, Lund University, Barngatan 4, 221 85, Lund, Sweden. mattias.belting@med.lu.se.; Department of Hematology, Oncology and Radiophysics, Skåne University Hospital, Lund, Sweden. mattias.belting@med.lu.se.
المصدر: Acta neuropathologica communications [Acta Neuropathol Commun] 2024 Feb 27; Vol. 12 (1), pp. 35. Date of Electronic Publication: 2024 Feb 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2013]-
مواضيع طبية MeSH: Glioblastoma*/pathology , Brain Neoplasms*/pathology, Adult ; Humans ; Hypoxia/metabolism ; Cell Line, Tumor ; Gene Expression Profiling ; Membrane Proteins ; Tumor Microenvironment
مستخلص: Immunotherapies with antibody-drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. We employed a comprehensive approach for global and dynamic profiling of the surfaceome and endocytosed (endocytome) proteins and their regulation by hypoxia in patient-derived GBM cultures. We found a heterogeneous surface-endocytome profile and a divergent response to hypoxia across GBM cultures. We provide a quantitative ranking of more than 600 surface resident and endocytosed proteins, and their regulation by hypoxia, serving as a resource to the cancer research community. As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. Among hypoxia induced proteins, we reveal CXADR, CD47, CD81, BSG, and FXYD6 as potential targets of the stressed GBM niche. We could validate these findings by immunofluorescence analyses in patient tumors and by increased expression in the hypoxic core of GBM spheroids. Selected candidates were finally confronted by treatment studies, showing their high capacity for internalization and ADC delivery. Importantly, we highlight the limited correlation between transcriptomics and proteomics, emphasizing the critical role of membrane protein enrichment strategies and quantitative mass spectrometry. Our findings provide a comprehensive understanding of the surface-endocytome and its remodeling by hypoxia in GBM as a resource for exploration of targets for immunotherapeutic approaches in GBM.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 23 2655 Pj Cancerfonden; 2023-02106 Vetenskapsrådet; PR2023-0078 Barncancerfonden; EU-MSCA-COFUND The CanFaster Program; 754299 The CanFaster Program
فهرسة مساهمة: Keywords: Glioblastoma; Hypoxia; Immunotherapy; Proteomics; Tumor antigens
المشرفين على المادة: 0 (Membrane Proteins)
تواريخ الأحداث: Date Created: 20240227 Date Completed: 20240229 Latest Revision: 20240229
رمز التحديث: 20240229
مُعرف محوري في PubMed: PMC10898066
DOI: 10.1186/s40478-024-01740-z
PMID: 38414005
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-5960
DOI:10.1186/s40478-024-01740-z