Antitumorigenic effect of interferon-beta by inhibition of undifferentiated glioblastoma cells

作者:Yamamuro Shun; Sano Emiko; Okamoto Yutaka; Ochiai Yushi; Ohta Takashi; Ogino Akiyoshi; Natsume Atsushi; Wakabayashi Toshihiko; Ueda Takuya; Hara Hiroyuki; Nakayama Tomohiro; Yoshino Atsuo*; Katayama Yoichi
来源:International Journal of Oncology, 2015, 47(5): 1647-1654.
DOI:10.3892/ijo.2015.3165

摘要

Glioma stem-like cells (GSCs) are undifferentiated cells that are considered to be an origin of glioblastomas. Furthermore, they may contribute to treatment resistance and recurrence in glioblastomas. GSCs differentiate into differentiated glioma cells (non-glioma stem-like cells: non-GSCs), and interconversion might occur between GSCs and non-GSCs. We investigated whether interferon-beta (IFN-beta) could exert any efficacy towards GSCs or such interconversion processes. The neural stem cell marker CD133 and pluripotency marker Nanog in GSCs were analyzed to evaluate their differentiation levels. GSCs were considered to undergo differentiation into non-GSCs upon serum exposure, since the expression of CD133 and Nanog in the GSCs was negatively affected. Furthermore, the cells regained their undifferentiated features upon removal of the serum. However, we verified that IFN-beta reduced cell proliferation and tumor sphere formation in GSCs, and induced suppression of the restoration of such undifferentiated features. In addition, we also confirmed that IFN-beta suppressed the acquisition process of undifferentiated features in human malignant glioma cell lines. Our data thus suggest that IFN-beta could be an effective agent not only through its cell growth inhibitory effect on GSCs but also as a means of targeting the interconversion between GSCs and non-GSCs, indicating the possibility of IFN-beta being used to prevent treatment resistance and recurrence in glioblastomas, via the inhibition of undifferentiated features.

  • 出版日期2015-11