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Sökning: id:"swepub:oai:lup.lub.lu.se:9a9c15e0-0419-4a70-b56e-7de18e30cea9" > Decoding of the sur...

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

de Oliveira, Kelin Gonçalves (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Bång-Rudenstam, Anna (författare)
Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Tumörmikromiljön,Research Group Lung Cancer,Lund University Research Groups,Tumor microenvironment,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Beyer, Sarah (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
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Boukredine, Axel (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Talbot, Hugo (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Governa, Valeria (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Johansson, Maria C (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Månsson, Ann-Sofie (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Forsberg Nilsson, Karin, 1963- (författare)
Uppsala universitet,Uppsala University,University of Nottingham,Science for Life Laboratory, SciLifeLab,Neuroonkologi och neurodegeneration,Univ Nottingham, Biodiscovery Inst, Div Canc & Stem Cells, Nottingham, England.
Bengzon, Johan (författare)
Lund University,Lunds universitet,Epilepsicentrum,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurokirurgi,Institutionen för kliniska vetenskaper, Lund,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Epilepsy Center,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Neurosurgery,Department of Clinical Sciences, Lund,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Lund Univ, Dept Clin Sci, Sect Neurosurg, Lund, Sweden.
Malmström, Johan (författare)
Lund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,BioMS,LTH profilområde: Teknik för hälsa,LTH profilområden,Lunds Tekniska Högskola,Lund University Research Groups,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH,Lund Univ, Dept Clin Sci, Div Infect Med, Lund, Sweden.
Welinder, Charlotte (författare)
Lund University,Lunds universitet,BioMS,Forskargrupper vid Lunds universitet,Lund University Research Groups,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.
Belting, Mattias (författare)
Lund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups,Skåne University Hospital,Lund Univ, Dept Clin Sci, Sect Oncol, Barngatan 4, S-22185 Lund, Sweden.;Skane Univ Hosp, Dept Hematol Oncol & Radiophys, Lund, Sweden.
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 (creator_code:org_t)
BioMed Central (BMC), 2024
2024
Engelska.
Ingår i: Acta Neuropathologica Communications. - : BioMed Central (BMC). - 2051-5960. ; 12:1
Relaterad länk:
http://dx.doi.org/10... (free)
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https://doi.org/10.1...
https://uu.diva-port... (primary) (Raw object)
https://lup.lub.lu.s...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Adult
Humans
Glioblastoma/pathology
Brain Neoplasms/pathology
Hypoxia/metabolism
Cell Line, Tumor
Gene Expression Profiling
Membrane Proteins
Tumor Microenvironment
Immunotherapy

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