PC3-Secreted Microprotein Is Expressed in Glioblastoma Stem-Like Cells and Human Glioma Tissues

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  • Maruyama Masato
    Department of Anatomy and Brain Science, Kansai Medical University
  • Nakano Yousuke
    Department of Anatomy and Brain Science, Kansai Medical University
  • Nishimura Takuya
    Department of Anatomy and Brain Science, Kansai Medical University
  • Iwata Ryoichi
    Department of Neurosurgery, Kansai Medical University
  • Matsuda Satoshi
    Department of Cell Signaling, Institute of Biomedical Science, Kansai Medical University
  • Hayashi Mikio
    Department of Physiology, Kansai Medical University
  • Nakai Yuki
    Department of Anatomy and Brain Science, Kansai Medical University
  • Nonaka Masahiro
    Department of Neurosurgery, Kansai Medical University
  • Sugimoto Tetsuo
    Department of Anatomy and Brain Science, Kansai Medical University

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Abstract

<p>Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor with a high recurrence rate. Despite multimodal therapy including surgical resection, chemotherapy, and radiotherapy, the median survival time after the initial diagnosis of GBM is approximately 14 months. Since cancer stem cells (CSCs) are considered the leading cause of cancer recurrence, glioblastoma stem cell-targeted therapy is a promising strategy for the treatment of GBM. However, because CSC heterogeneity has been implicated in the difficulties of CSC-target therapy, more in-depth knowledge of CSC biology is still required to develop novel therapies. In this study, we established single cell-derived tumorspheres from human glioblastoma U87MG cells. One of these tumorspheres, P4E8 clone, showed CSC-like phenotypes, such as self-renewal capacity, expression of CSC markers, resistance to anti-cancer agents, and in vivo tumorigenicity. Therefore, we used P4E8 cells as a cell-based model of glioblastoma stem cells (GSCs). Gene expression analysis using microarray indicated that the most highly expressed genes in P4E8 cells compared to the parental U87MG were PC3-secreted microprotein (MSMP). Furthermore, MSMP was expressed in patient-derived GSCs and human glioma tissues at the protein level, implying that MSMP might contribute to glioma development and progression.</p>

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