Resolving the stem-cell debate

Abstract

New research backs the contentious idea that solid tumours are not masses of equivalent cells, but instead contain cancer stem cells that support tumour maintenance. Here, two experts provide complementary views on the findings and on the implications for potential therapies. See Letters p.522 & p.527 In a mouse model of glioblastoma, Luis Parada and colleagues use a green fluorescent protein (GFP) reporter protein expressed selectively in neural stem cells — in which the tumours arise — to trace cancer cells in an endogenous setting. The reporter labelled a small subset of glioma cells that were less proliferative than the bulk of the tumour cells. However, the GFP+ cells were responsible for re-growth of the tumours after treatment with the cytotoxic drug temozolomide. Selective ablation of the GFP+ cells combined with temozolomide was more effective at arresting tumour growth. The GFP+ cells appear to be at the apex of a functional hierarchy of cancer cells so may represent cancer stem cells — a subset of tumour cells able to maintain tumour growth. Targeting both this population and the more proliferative bulk of cancer cells may lead to improved therapeutic outcome. Using genetic-lineage tracing, Cedric Blanpain and colleagues for the first time clonally trace tumour cells in vivo in an unperturbed solid tumour. In a carcinogen-induced papilloma mouse model, they find that the cells in these benign lesions mirror the clonal hierarchy organization of normal tissue. Only a fraction of papilloma cells with a higher proliferative potential is able to sustain a second, slower-cycling transient population that gives rise to the differentiated tumour cells that form the bulk of the papillomas. But when lesions progress to squamous cell carcinomas, there is a switch to mainly self-renewing divisions and limited differentiation, suggesting that these cells may represent a cancer stem cell population. Evidence for cancer stem cells — a subset of tumour cells able to maintain tumour growth — has previously been demonstrated only in solid tumours in transplantation experiments.