Na+/K+-ATPase b2-subunit (AMOG) expression abrogates invasion of glioblastoma-derived brain tumor-initiating cells

Matthew Z. Sun, Joseph M. Kim, Michael C. Oh, Michael Safaee, Gurvinder Kaur, Aaron J. Clark, Orin Bloch, Michael E. Ivan, Rajwant Kaur, Taemin Oh, Shaun D. Fouse, Joanna J. Phillips, Mitchel S. Berger, Andrew T. Parsa

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background. Mechanisms of glioma invasion remain to be fully elucidated. Gliomacells within glioblastoma multiforme (GBM) range from well-differentiated tumor cells to less-differentiated brain tumor-initiating cells (BTICs). The b2-subunit of Na+ /K+-ATPase, called the adhesion molecule on glia (AMOG), is highly expressed in normal glia but is thought to be universally downregulated in GBM. To test our hypothesis that expression of AMOG is heterogeneous in GBM and confers a less invasive phenotype, we compared it between BTICs and differentiated cells from patient-matched GBM and then tested GBM invasion in vitro after AMOG overexpression. Methods. Immunohistochemistry, immunoblotting, and real-time PCR were used to characterize AMOG protein andmRNA expression in tumor samples, BTICs, and differentiated cells. Matrigel invasion assay, scratch assay, and direct cell counting were used for testing in vitro invasion, migration, and proliferation, respectively. Results. WhileAMOGexpression is heterogeneous in astrocytomas of grades II-IV, it is lost in mostGBM. BTICs express higher levels ofAMOG mRNA and protein compared with patient-matched differentiated tumor cells. Overexpression of AMOG decreased GBM cell and BTIC invasion without affecting migration or proliferation. Knockdown of AMOG expression in normal human astrocytes increased invasion. Conclusions. AMOGexpression inhibitsGBMinvasion. Its downregulation increases invasion in glial cells and may also represent an important step in BTIC differentiation. These data provide compelling evidence implicating the role of AMOG in glioma invasion and provide impetus for further investigation.

Original languageEnglish (US)
Pages (from-to)1518-1531
Number of pages14
JournalNeuro-Oncology
Volume15
Issue number11
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

Keywords

  • AMOG
  • Brain tumor-initiating cells
  • Glioblastoma
  • Invasion
  • Na/K-ATPase b2-subunit

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Sun, M. Z., Kim, J. M., Oh, M. C., Safaee, M., Kaur, G., Clark, A. J., Bloch, O., Ivan, M. E., Kaur, R., Oh, T., Fouse, S. D., Phillips, J. J., Berger, M. S., & Parsa, A. T. (2013). Na+/K+-ATPase b2-subunit (AMOG) expression abrogates invasion of glioblastoma-derived brain tumor-initiating cells. Neuro-Oncology, 15(11), 1518-1531. https://doi.org/10.1093/neuonc/not099