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 language | English (US) |
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Pages (from-to) | 72021-72032 |
Number of pages | 12 |
Journal | Oncotarget |
Volume | 7 |
Issue number | 44 |
DOIs | |
State | Published - 2016 |
Keywords
- Cancer therapeutic target
- Cell surface vimentin
- Glioblastoma multiforme
- Tumor initiating cells
ASJC Scopus subject areas
- Oncology
MD Anderson CCSG core facilities
- Monoclonal Antibody Facility
- Advanced Technology Genomics Core
- Research Animal Support Facility
- Cytogenetics and Cell Authentication Core