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PXD048880

PXD048880 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDecoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor nicheDecoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche
DescriptionImmunotherapies 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:42:01.541.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCharlotte Welinder
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-25 06:27:02ID requested
12024-05-23 01:27:39announced
22024-10-22 06:42:02announced2024-10-22: Updated project metadata.
Publication List
10.1186/s40478-024-01740-z;
Keyword List
submitter keyword: glioblastoma, tumor antigens, proteomics, hypoxia.,Immunotherapy
Contact List
Kelin Goncalves de Oliveira
contact affiliationDepartment of Clinical Sciences Lund, Section of Oncology, Lund University, Lund 221 85, Sweden
contact emailkelin.goncalves_de_oliveira@med.lu.se
lab head
Charlotte Welinder
contact affiliationDept. of Oncology, Clinical Sciences, Lund University, 221 85 Lund, Sweden
contact emailcharlotte.welinder@med.lu.se
dataset submitter
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Dataset FTP location
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