Discovery of cell surface vimentin targeting mAb for direct disruption of GBM tumor initiating cells
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Hyangsoon Noh1, Jun Yan1, Sungguan Hong2, Ling-Yuan Kong3, Konrad Gabrusiewicz3, Xueqing Xia1, Amy B. Heimberger3, Shulin Li1
1Department of Pediatrics–Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
3Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Shulin Li, email: Sli4@mdanderson.org
Amy B. Heimberger, email: firstname.lastname@example.org
Keywords: cell surface vimentin, glioblastoma multiforme, tumor initiating cells, cancer therapeutic target
Received: August 04, 2016 Accepted: September 29, 2016 Published: October 04, 2016
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.
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