title: Discovery of cell surface vimentin targeting mAb for direct disruption of GBM tumor initiating cells.
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.
authors.affiliation: Department of Pediatrics-Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hyangsoon
authors.initials: H
authors.lastname: Noh
authors.affiliation: Department of Pediatrics-Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sungguan
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ling-Yuan
authors.initials: LY
authors.lastname: Kong
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Gabrusiewicz
authors.affiliation: Department of Pediatrics-Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
authors.affiliation: Department of Pediatrics-Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Shulin
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D018874:Spheroids, Cellular; D014746:Vimentin / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D014746:Vimentin; D053148:Caspase 3
keywords: cancer therapeutic target; cell surface vimentin; glioblastoma multiforme; tumor initiating cells