Identification of a cancer stem cell in human brain tumors.

TLDR

Human brain tumors are typically studied at the bulk level, yet evidence shows tumor heterogeneity and a hierarchical organization similar to leukemia, where rare stem cells drive proliferation and differentiation. The study aims to identify and isolate a brain tumor stem cell to enable investigation of tumorigenesis and development of targeted therapies. The authors isolated CD133⁺ brain tumor stem cells that exhibit high proliferation, self‑renewal, and differentiation, with the strongest self‑renewal seen in aggressive medulloblastoma samples, and these cells can generate tumor cells resembling the patient’s tumor.

Abstract

Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.