Cancer stem cells from peritumoral tissue of glioblastoma multiforme: The possible missing link between tumor development and progression

Cristiana Angelucci, Alessio D'Alessio, Gina Lama, Elena Binda, Annunziato Mangiola, Angelo L. Vescovi, Gabriella Proietti, Laura Masuelli, Roberto Bei, Barbara Fazi, Silvia Anna Ciafrè, Gigliola Sica

Research output: Contribution to journalArticle

Abstract

In glioblastoma multiforme (GBM), cancer stem cells (CSCs) are thought to be responsible for gliomagenesis, resistance to treatment and recurrence. Unfortunately, the prognosis for GBM remains poor and recurrence frequently occurs in the peritumoral tissue within 2 cm from the tumor edge. In this area, a population of CSCs has been demonstrated which may recapitulate the tumor after surgical resection. In the present study, we aimed to characterize CSCs derived from both peritumoral tissue (PCSCs) and GBM (GCSCs) in order to deepen their significance in GBM development and progression. The stemness of PCSC/GCSC pairs obtained from four human GBM surgical specimens was investigated by comparing the expression of specific stem cell markers such as Nestin, Musashi-1 and SOX2. In addition, the growth rate, the ultrastructural features and the expression of other molecules such as c-Met, pMet and MAP kinases, involved in cell migration/invasion, maintenance of tumor stemness and/or resistance to treatments were evaluated. Since it has been recently demonstrated the involvement of the long noncoding RNAs (lncRNAs) in the progression of gliomas, the expression of H19 lncRNA, as well as of one of its two mature products miR-675-5p was evaluated in neurospheres. Our results show significant differences between GCSCs and PCSCs in terms of proliferation, ultrastructural peculiarities and, at a lower extent, stemness profile. These differences might be important in view of their potential role as a therapeutic target.

Original languageEnglish
Pages (from-to)28116-28130
Number of pages15
JournalOncotarget
Volume9
Issue number46
DOIs
Publication statusPublished - Jun 15 2018

Keywords

  • Glioblastoma cancer stem cells
  • H19 lncRNA and miR-675-5p
  • Peritumoral cancer stem cells
  • Proliferation and invasiveness markers
  • Stemness markers

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Angelucci, C., D'Alessio, A., Lama, G., Binda, E., Mangiola, A., Vescovi, A. L., Proietti, G., Masuelli, L., Bei, R., Fazi, B., Ciafrè, S. A., & Sica, G. (2018). Cancer stem cells from peritumoral tissue of glioblastoma multiforme: The possible missing link between tumor development and progression. Oncotarget, 9(46), 28116-28130. https://doi.org/10.18632/oncotarget.25565