Figure 1. Cellular hierarchy in normal tissue and tumour. In a normal tissue (left), there is a small population of largely quiescent stem cells (SC), which both self-renew and, by the process of asymmetric cell division, give rise to an intensively proliferating committed progenitor – the transit amplifying (TA) cell. The TA cells finally cease their proliferation and yield terminally differentiated cells (TDC), which are largely responsible for the respective tissue function. Analogical processes are supposed to be operating in a tumour as well (right). Accordingly, cancer stem cells (CSC) are exclusively responsible for the self-renewing of the tumour cell population, whereas cancerous transit amplifying (CTA) cells would make up a bulk of cancer cells. A corrupted differentiation might take place to a variable extent in tumours as well, sometimes producing cells resembling differentiated cells of the tissue of origin of the tumour in question (DC). Besides, the pseudodifferentiation of CTA cells can lead to a diversification of tumour cells, resulting in the expression of different transformation-related traits in different cell subpopulations, here schematically illustrated as an angiogenic cell (AC), invasive cell (IC) and autonomously growing cell (AGC). This is not to say that the expression of these properties is mutually exclusive; in reality, many transformation-related traits are variably coexpressed by majority of tumour cells. The cancer stem cell usually originates from a mutated respective tissue stem cell and the somatic mutagenesis (yellow flesh lighting) continues to be present along all stages of cancerous pseudodifferentiation, further enhancing the final diversity of tumour cells. Reproduced from Hatina et al. (2007) Tumour stem cells – a new concept in tumour biology (in German). Deutsche Medizinische Wochenschrift 132: 1629–1632, by permission of Georg Thieme Verlag KG.

Figure 2. Therapeutic implications of the cancer stem cell concept. Traditional tumour therapy especially targets rapidly proliferating tumour cells. This often leads to impressive clinical responses or even complete clinical remissions. Cancer stem cells, however, frequently survive this treatment, thanks to their low proliferative activity as well as their intrinsic chemoresistance, finally resulting in a disease relapse. Cancer stem cell-based therapy, however, possesses a potential to be curative, because the elimination of the cancer stem cells would leave the patient with a population of tumour cells that cannot self-renew. Crucial for the feasibility of the cancer stem cell-based therapy is that respective normal stem cells are not fatally damaged. Reproduced from Hatina et al. (2007) Tumour stem cells – a new concept in tumour biology (in German). Deutsche Medizinische Wochenschrift 132: 1629–1632, by permission of Georg Thieme Verlag KG.