The Cell Surface Proteome of Malignant Peripheral Nerve Sheath Tumors Reveals Therapeutic Targets

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ID: 321749
2026
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Ranked #26 of 104 articles by views in Neuro-Oncology Advances

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Abstract
Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas and the most common cause of disease-associated death for Neurofibromatosis Type 1 (NF1) patients. In the context of NF1, MPNSTs develop from benign premalignant precursors. The transition to malignancy is usually accompanied by loss of the polycomb repressive complex 2 (PRC2), leading to aberrant upregulation of many genes. There is a significant gap in our knowledge of which cell-surface targets become derepressed and therapeutically actionable following PRC2 loss, contributing to the current lack of effective targeted therapies for MPNSTs. Methods This study uses cell-surface capture technology with mass spectrometry to profile MPNST models. We define PRC2-dependent effects on the cell surface proteome by profiling models with and without PRC2 activity and comparing surface protein profiles. We also create an MPNST cell-surface protein compendium comprised of proteins that are highly expressed across a variety of well-defined MPNST models. Results Comparisons of PRC2-active to PRC2-inactive samples revealed a host of pathways dysregulated on the surface protein level, including epithelial-mesenchymal transition and interferon response. A MPNST cell surface protein compendium was defined with multiple previously known and unknown surface antigens. These markers made tumor-derived cell lines vulnerable to therapeutic assault and showed significant presence in immunostaining of primary MPNST samples. Conclusion Results reveal PTK7 as a novel and promising target for MPNST. In total, these efforts represent a step toward addressing the knowledge gap in MPNST genesis and identifying new therapeutic targets for further testing.
Reference Key
openalex_W7169838197 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Christopher M. Stehn, Liangjun Wang, Davis Seelig, Zach Seeman, David A. Largaespada
Journal Neuro-Oncology Advances
Year 2026
DOI
10.1093/noajnl/vdag189
URL
https://doi.org/10.1093/noajnl/vdag189
Keywords Keywords not found

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