Discovery of cell surface vimentin targeting mAb for direct disruption of GBM tumor initiating cells.
Discovery of cell surface vimentin targeting mAb for direct disruption of GBM tumor initiating cells.
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DOI：
10.18632/oncotarget.12458
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Li S
中科院分区：
文献类型：
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作者：
Noh H;Yan J;Hong S;Kong LY;Gabrusiewicz K;Xia X;Heimberger AB;Li S
细胞内波形蛋白的过度表达与上皮-间充质转化、转移、侵袭和增殖有关，但对细胞表面波形蛋白(CSV)的了解较少。此外，目前尚不清楚CSV是否可以作为表达CSV的肿瘤细胞的治疗靶点。我们发现CSV存在于多形性胶质母细胞瘤(GBM)肿瘤干细胞上，并且CSV的表达与这些细胞中球体的形成有关。新近研制的抗CSV单抗86C在体外可显著诱导GBM细胞凋亡并抑制球体的形成。体外培养的GBM细胞加入86C后，细胞内Vimentin迅速内化，细胞活力下降。这些发现与caspase-3活性增加有关，表明细胞凋亡被激活。最后，86C治疗在体内抑制了GBM的进展。综上所述，表达CSV的GBM细胞具有肿瘤起始细胞的特性，用86C单抗靶向CSV是治疗GBM的一种有前景的方法。
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.