Discovery of cell surface vimentin targeting mAb for direct disruption of GBM tumor initiating cells

Hyangsoon Noh, Jun Yan, Sungguan Hong, Ling Yuan Kong, Konrad Gabrusiewicz, Xueqing Xia, Amy B. Heimberger, Shulin Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Intracellular vimentin overexpression has been associated with epithelial- mesenchymal transition, metastasis, invasion, and proliferation, but cell surface vimentin (CSV) is less understood. Furthermore, it remains unknown whether CSV can serve as a therapeutic target in CSV-expressing tumor cells. We found that CSV was present on glioblastoma multiforme (GBM) cancer stem cells and that CSV expression was associated with spheroid formation in those cells. A newly developed monoclonal antibody against CSV, 86C, specifically and significantly induced apoptosis and inhibited spheroid formation in GBM cells in vitro. The addition of 86C to GBM cells in vitro also led to rapid internalization of vimentin and decreased GBM cell viability. These findings were associated with an increase in caspase-3 activity, indicating activation of apoptosis. Finally, treatment with 86C inhibited GBM progression in vivo. In conclusion, CSV-expressing GBM cells have properties of tumor initiating cells, and targeting CSV with the monoclonal antibody 86C is a promising approach in the treatment of GBM.

Original languageEnglish (US)
Pages (from-to)72021-72032
Number of pages12
JournalOncotarget
Volume7
Issue number44
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • Cancer therapeutic target
  • Cell surface vimentin
  • Glioblastoma multiforme
  • Tumor initiating cells

ASJC Scopus subject areas

  • Oncology

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