A BMP7 variant inhibits the tumorigenic potential of glioblastoma stem-like cells

Roberto Pallini, Stefano Giannetti, Luigi Maria Larocca, Ruggero De Maria Marchiano, Liliana Morgante, Susanna Di Martino, C. M. Tate, L. Ricci-Vitiani, M. Dowless, T. Shiyanova, S. Di Martino, S. W. Rowlinson, L. Stancato

Risultato della ricerca: Contributo in rivistaArticolo in rivista

46 Citazioni (Scopus)

Abstract

Glioblastoma multiforme (GBM) is among the most aggressive tumor types and is essentially an incurable malignancy characterized by resistance to chemo-, radio-, and immunotherapy. GBM is maintained by a hierarchical cell organization that includes stem-like, precursor, and differentiated cells. Recurrence and maintenance of the tumor is attributed to a small population of undifferentiated tumor-initiating cells, defined as glioblastoma stem-like cells (GSLCs). This cellular hierarchy offers a potential treatment to induce differentiation of GSLCs away from tumor initiation to a more benign phenotype or to a cell type more amenable to standard therapies. Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have numerous biological activities including control of growth and differentiation. In vitro, a BMP7 variant (BMP7v) decreased primary human GSLC proliferation, endothelial cord formation, and stem cell marker expression while enhancing neuronal and astrocyte differentiation marker expression. In subcutaneous and orthotopic GSLC xenografts, which closely reproduce the human disease, BMP7v decreased tumor growth and stem cell marker expression, while enhancing astrocyte and neuronal differentiation compared with control mice. In addition, BMP7v reduced brain invasion, angiogenesis, and associated mortality in the orthotopic model. Inducing differentiation of GSLCs and inhibiting angiogenesis with BMP7v provides a potentially powerful and novel approach to the treatment of GBM. © 2012 Macmillan Publishers Limited All rights reserved.
Lingua originaleEnglish
pagine (da-a)1644-1654
Numero di pagine11
RivistaCell Death and Differentiation
Volume19
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Animals
  • Bone Morphogenetic Protein 7
  • Brain Neoplasms
  • Cell Biology
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytokines
  • Glioblastoma
  • HCT116 Cells
  • Humans
  • Mice
  • Molecular Biology
  • Neoplastic Stem Cells
  • Neovascularization, Pathologic
  • Transplantation, Heterologous
  • bone morphogenetic protein
  • cancer stem cells

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