Proteomic Analysis Reveals Drug Accessible Cell Surface N‑Glycoproteins of Primary and Established Glioblastoma Cell Lines

Glioblastoma is the most common primary 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.