title: Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers.
abstract: Glioblastoma multiforme (GBM), the grade IV astrocytoma, is the most common and aggressive brain tumor in adults. Despite advances in medical management, the survival rate of GBM patients remains poor, suggesting that identification of GBM-specific targets for therapeutic development is urgently needed. Analysis of several glycan antigens on GBM cell lines revealed that eight of 11 GBM cell lines are positive for stage-specific embryonic antigen-4 (SSEA-4), and immunohistochemical staining confirmed that 38/55 (69%) of human GBM specimens, but not normal brain tissue, were SSEA-4(+) and correlated with high-grade astrocytoma. In addition, an SSEA-4-specific mAb was found to induce complement-dependent cytotoxicity against SSEA-4(hi) GBM cell lines in vitro and suppressed GBM tumor growth in mice. Because SSEA-4 is expressed on GBM and many other types of cancers, but not on normal cells, it could be a target for development of therapeutic antibodies and vaccines.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Lou
authors.forename: Pao-Yuan
authors.initials: PY
authors.lastname: Wang
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Yeh
authors.forename: Po-Kai
authors.initials: PK
authors.lastname: Chuang
authors.forename: Shiou-Ting
authors.initials: ST
authors.lastname: Li
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D055746:Stage-Specific Embryonic Antigens / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D055746:Stage-Specific Embryonic Antigens; C066584:stage-specific embryonic antigen-4
keywords: Globo H; SSEA-3; gangliosides; glycosphingolipids; targeted therapy