title: CD166/activated leukocyte cell adhesion molecule is expressed on glioblastoma progenitor cells and involved in the regulation of tumor cell invasion.
abstract: For improvement of prognosis for glioblastoma patients, which remains poor, identification and targeting of glioblastoma progenitor cells are crucial. In this study, we found that the cluster of differentiation (CD)166/activated leukocyte cell adhesion molecule (ALCAM) was highly expressed on CD133+ glioblastoma progenitor cells. ALCAM+ CD133+ cells were highly enriched with tumor sphere-initiating cells in vitro. Among gliomas with isocitrate dehydrogenase-1/R132H mutation, the frequencies of ALCAM+ cells were significantly higher for glioblastomas than for World Health Organization grade II or III gliomas. The function of ALCAM in glioblastoma was then investigated. An in vitro invasion assay showed that transfection of ALCAM small interfering RNA or small hairpin RNA into glioblastoma cells significantly increased cell invasion without affecting cell proliferation. A soluble isoform of ALCAM (sALCAM) was also expressed in all glioblastoma samples and at levels that correlated well with ALCAM expression levels. In vitro invasion of glioblastoma cells was significantly enhanced by administration of purified sALCAM. Furthermore, overexpression of sALCAM in U87MG glioblastoma cells promoted tumor progression in i.c. transplants into immune-deficient mice. In summary, we were able to show that ALCAM constitutes a novel glioblastoma progenitor cell marker. We could also demonstrate that ALCAM and its soluble isoform are involved in the regulation of glioblastoma invasion and progression.
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kijima
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.forename: Naoki
authors.initials: N
authors.lastname: Kagawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakano
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human