title: Epithelial membrane protein-2 (EMP2) activates Src protein and is a novel therapeutic target for glioblastoma.
abstract: Despite recent advances in molecular classification, surgery, radiotherapy, and targeted therapies, the clinical outcome of patients with malignant brain tumors remains extremely poor. In this study, we have identified the tetraspan protein epithelial membrane protein-2 (EMP2) as a potential target for glioblastoma (GBM) killing. EMP2 had low or undetectable expression in normal brain but was highly expressed in GBM as 95% of patients showed some expression of the protein. In GBM cells, EMP2 enhanced tumor growth in vivo in part by up-regulating αvβ3 integrin surface expression, activating focal adhesion kinase and Src kinases, and promoting cell migration and invasion. Consistent with these findings, EMP2 expression significantly correlated with activated Src kinase in patient samples and promoted tumor cell invasion using intracranial mouse models. As a proof of principle to determine whether EMP2 could serve as a target for therapy, cells were treated using specific anti-EMP2 antibody reagents. These reagents were effective in killing GBM cells in vitro and in reducing tumor load in subcutaneous mouse models. These results support the role of EMP2 in the pathogenesis of GBM and suggest that anti-EMP2 treatment may be a novel therapeutic treatment.
authors.affiliation: From the Departments of Ophthalmology and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Maoyong
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095 and.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Akio
authors.initials: A
authors.lastname: Iwanami
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kuga
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Rajiv G
authors.initials: RG
authors.lastname: Rao
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Sudhakar
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Huang
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Meagan
authors.initials: M
authors.lastname: Kiyohara
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Torres
authors.affiliation: Pathology and Laboratory Medicine.
authors.forename: Christen
authors.initials: C
authors.lastname: Dillard
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095 and.
authors.forename: Akihito
authors.initials: A
authors.lastname: Inagaki
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095 and.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasahara
authors.affiliation: Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, and.
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
authors.affiliation: Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.affiliation: the Ludwig Institute for Cancer Research, Department of Pathology, University of California at San Diego, La Jolla, California 92093.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Mischel
authors.affiliation: From the Departments of Ophthalmology and.
authors.forename: Lynn K
authors.initials: LK
authors.lastname: Gordon
authors.affiliation: Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, and mwadehra@mednet.ucla.edu.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Wadehra
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy; D010641:Phenotype; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C486403:EMP2 protein, human; D008562:Membrane Glycoproteins; D051417:Focal Adhesion Kinase 1; D019061:src-Family Kinases
keywords: Cell Invasion; EMP2; Glioblastoma; Immunotherapy; Tetraspanins; Tumor Marker