Identification of human brain tumor initiating cells

The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Canada.
Nature (Impact Factor: 41.46). 12/2004; 432(7015):396-401. DOI: 10.1038/nature03128
Source: PubMed


The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. 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 10(5) 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 tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.

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    • "Experimental evidence supporting the cancer stem cells (CSCs, also known as tumour-initiating or tumour-propagating cells) hypothesis was first generated in 1997 by Dick's group, who documented that human acute myeloid leukaemia (AML) was driven by a small fraction of CD34 þ /CD38 e leukaemic stem cells capable of transferring the disease to severe combined immunodeficiency disease (SCID) recipient mice [4,5]. Increasing data over recent years have indicated the existence of CSCs in a broad spectrum of solid carcinomas, including breast [6,7], brain [8], lung [9], colon [10e12], liver [13], and pancreatic cancers [14], based on their efficient tumour-initiating capabilities upon xenotransplantation into mice after isolation from primary tumours. Critics have argued that previous studies examined the existence and function of CSCs using transplantation models but not in a natural settings [15]. "
    Full-text · Dataset · Apr 2016
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    • "In the case of GBM, this vast heterogeneity is also exemplified by the presence of a subpopulation of cancer initiating cells with stemlike potential called glioma stemlike cells (GSC). GSC and their glioma differentiated cell (GDC) counterpart would be the two extremes of the spectrum of variability comprising the highly heterogeneous GBM mass in vivo [10, 11, 14, 15]. The proportion of this cancer stemlike cell population in the tumor mass is proposed to be an indication of the tumor aggressivity and of a poor prognosis [13, 16]. "
    Full-text · Dataset · Apr 2016
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    • "Results from that study demonstrated that the CD34 + CD38´populationCD38´CD38´population of cells caused disease more frequently and at lower cell numbers than CD34´cellsCD34´CD34´cells [75]. Subsequent to these findings, CSCs have been described in many solid tumors including those of the brain, prostate, breast, colon, and pancreas [76][77][78][79][80][81]. In addition to being responsible for primary tumor formation, CSCs are also generally thought to drive metastasis and exhibit increased resistance to radiation and chemotherapy. "
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    Full-text · Article · Apr 2016
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