Identification of human brain tumour initiating cells

Abstract

The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties^1,2. Although the existence of CSCs in human leukaemia is established^3,4, little evidence exists for CSCs in solid tumours, except for breast cancer⁵. Recently, we prospectively isolated a CD133⁺ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro⁶. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour^1,2,7. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133⁺ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133⁺ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10⁵ CD133^- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours⁵, and establishes a previously unidentified cellular target for more effective cancer therapies.