Glioma stem cells: a midterm exam.

Several years ago, the discovery of a highly tumorigenic subpopulation of stem-like cells embedded within fresh surgical isolates of malignant gliomas lent support to a new paradigm in cancer biology--the cancer stem cell hypothesis. At the same time, these "glioma stem cells" seemed to resolve a long-standing conundrum on the cell of origin for primary cancers of the brain. However, central tenets of the cancer stem cell hypothesis have recently been challenged, and the cellular origins of stem-like cells within malignant glioma are still contended. Here, we summarize the issues that are still in play with respect to the cancer stem cell hypothesis, and we revisit the developmental origins of malignant glioma. Do glioma stem cells arise from developmentally stalled neural progenitors or from dedifferentiated astrocytes? Five separate predictions of a neural progenitor cell of origin are put to the test.