Human brain tumor stem cells

Recent findings in stem cell research have demonstrated the existence of cancer stem cells in leukemia and also in solid tumors such as those of the brain, mainly in glioblastoma multiforme (GBM) and perhaps in medulloblastomas (MDBs) and ependymomas (EPMs). These cells could be defined as cancer stem cells because they show a degree of similarity with their normal counterpart, such as the ability to self-renew and differentiate into the cell lineages typical of the tissue of origin. In particular, brain tumor stem cells isolated from human GBM satisfy all of the expected stem cell features: they self-renew under clonal conditions, proliferate in vitro for long periods of time and differentiate into neuron- and glia-like cells as well as into abnormal cells, with aberrant, mixed neuronal/astroglia phenotypes. The ability to generate all of the cell types of the tissue of origin in vivo results in the development of serially transplantable tumors - which are faithful phenocopies of the original human pathology - upon orthotopic injection into immunodeficient mice. From this standpoint, the first and most critical need in the newborn brain cancer stem cell field is the identification of selective markers and molecular mechanisms that underpin the tumorigenic potential of these cells. This would allow us to devise new therapeutic strategies for the treatment of malignant brain tumors, in particular GBM. The recent discovery that bone morphogenetic proteins inhibit the tumorigenic potential of cancer stem cells derived from GBMs, by promoting the acquisition of a more differentiated phenotype, suggests that new, noncytotoxic, pro-differentiation therapies may be established in the future. These treatments could be used in combination with conventional therapies to curb tumor progression and recurrence.