Tumour stem cells--the evidence and the ambiguity

Progressive growth of malignant tumours, metastatic spread and local recurrence after treatment can only be explained by the presence of cells with unlimited proliferative ability. While this is generally accepted, the proportion of such cells and their organization in a hierarchical system of stem cells and non-stem cell progeny is still a matter of controversy. Results of quantitative transplantation and dose requirement of curative radiotherapy have indicated low stem cell fractions in human and early passage rodent tumours, but uncertainty is introduced by uncontrollable experimental or biological factors and the probabilistic nature of stem cell performance itself. Studies using a particular mouse carcinoma (AT17) have given direct insight into the number and clonal expansion of stem cells in situ, strongly supporting the hierarchical concept. The implications are important and concern the relevance of predictive assays, possible mechanisms of accelerated repopulation, or the role of adjuvant treatment strategies.