CD166/activated leukocyte cell adhesion molecule is expressed on glioblastoma progenitor cells and involved in the regulation of tumor cell invasion

Neuro Oncol. 2012 Oct;14(10):1254-64. doi: 10.1093/neuonc/nor202. Epub 2011 Dec 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / chemistry
  • Activated-Leukocyte Cell Adhesion Molecule / genetics
  • Activated-Leukocyte Cell Adhesion Molecule / metabolism*
  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Movement*
  • Cell Proliferation*
  • Flow Cytometry
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Male
  • Mice
  • Mice, SCID
  • Mutation / genetics
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Activated-Leukocyte Cell Adhesion Molecule
  • RNA, Messenger
  • RNA, Small Interfering
  • Isocitrate Dehydrogenase
  • IDH1 protein, human