Journal
JOURNAL OF PROTEOME RESEARCH
Volume 11, Issue 10, Pages 4885-4893Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr300360a
Keywords
glioblastoma; N-glycoproteins; cell surface accessible drug targets; cell surface capturing; N-glycoproteome SRM library
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Funding
- National Center of Competence in Research (NCCR) Neural Plasticity and Repair
- SystemsX.ch/BIP project
- SystemsX.ch/InfectX project within the Swiss Initiative in Systems Biology
- European Research Council [ERC-2008-AdG 233226]
- Swiss National Science Foundation [31003A-130530]
- Zentrum fur Neurowissenschaften Zurich (ZNZ)
- Swiss National Science Foundation (SNF) [31003A_130530] Funding Source: Swiss National Science Foundation (SNF)
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Glioblastoma is the most common primary Glioblastoma Cell Surface Capturing brain tumor in adults with low average survival time after diagnosis. In order to improve glioblastoma treatment, new drug-accessible targets need to be identified. Cell surface glycoproteins are prime drug targets due to their accessibility at the surface of cancer cells. To overcome the limited availability of suitable antibodies for cell surface protein detection, we performed a comprehensive mass spectrometric investigation of the glioblastoma surfaceome. Our combined cell surface capturing analysis of primary ex vivo glioblastoma cell lines in combination with established glioblastoma cell lines revealed 633 N-glycoproteins, which vastly extends the known data of surfaceome drug targets at subcellular resolution. We provide direct evidence of common glioblastoma cell surface glycoproteins and an approximate estimate of their abundances, information that could not be derived from genomic and/or transcriptomic glioblastoma studies. Apart from our pharmaceutically valuable repertoire of already and potentially drug-accessible cell surface glycoproteins, we built a mass-spectrometry-based toolbox enabling directed, sensitive, and repetitive glycoprotein measurements for clinical follow-up studies. The included Skyline Glioblastoma SRM assay library provides an elevated starting point for parallel testing of the abundance level of the detected glioblastoma surfaceome members in future drug perturbation experiments.
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