Transferrin receptor 2 is frequently and highly expressed in glioblastomas

Luigi Maria Larocca, Francesco Pierconti, Ruggero De Maria Marchiano, Roberto Pallini, Alessia Calzolari, Silvia Deaglio, Veronica Finisguerra, Alessandra Boe, Carla Raggi, Lucia Ricci-Vitani, Fabio Malavasi, Ugo Testa

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Under physiological conditions, transferrin receptor 2 (TfR2) is expressed in the liver and its balance is related to the cell cycle rather than to intracellular iron levels. We recently showed that TfR2 is highly expressed in glioblastoma cell lines. Here, we demonstrate that, in these cells, TfR2 appears to localize in lipid rafts, induces extracellular signal-regulated kinase 1/2 phosphorylation after transferrin binding, and contributes to cell proliferation, as shown by RNA silencing experiments. In vitro hypoxic conditions induce a significant TfR2 up-regulation, suggesting a role in tumor angiogenesis. As assessed by immunohistochemistry, the level of TfR2 expression in astrocytic tumors is related to histologic grade, with the highest expression observed in glioblastomas. The level of TfR2 expression represents a favorable prognostic factor, which is associated with the higher sensitivity to temozolomide of TfR2-positive tumor cells in vitro. The endothelial cells of glioblastoma vasculature also stain for TfR2, whereas those of the normal brain vessels do not. Importantly, TfR2 is expressed by the subpopulation of glioblastoma cells with properties of cancerinitiating cells. TfR2-positive glioblastoma cells retain their TfR2 expression on xenografting in immunodeficient mice. In conclusion, our observations demonstrate that TfR2 is a neoantigen for astrocytomas that seems attractive for developing target therapies. Copyright © 2010 Neoplasia Press, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)123-134
Number of pages12
JournalTranslational Oncology
Volume3
DOIs
Publication statusPublished - 2010

Keywords

  • Cancer Research
  • Oncology

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