Tumor stem cells: How to define them and how to find them?

Abstract

Cancer stem cells like normal tissue stem cells have the ability to selfrenew and to perform asymmetric division creating another malignant stem cell and a cell that gives rise to the phenotypically diverse tumor cell population. The hypothesis that cancer depends on a small population of cancer stem cells for its continued growth and propagation exists since Virchow proposed that cancer arises from embryo-like cells in 1858 and was further developed parallel to the development of analytical methods. To this day specific changes in cellular pathways and in the expression of surface markers have been found in leukaemia stem cells as well as in pancreatic, hepato-biliary, colon, brain, breast, ovarian, prostate, melanoma and lung cancer, nasopharyngeal tumors, laryngeal tumors and retinoblastomas as examples of solid tumors containing tumor stem cells. In cancer stem cells, developmental pathways are believed to be deregulated leading to uncontrolled self-renewal of cancer stem cells which generate tumors that are resistant to conventional therapies. Cancer stem cells as normal stem cells are likely to depend on a stem cell niche, a specialized microenvironment in which stem cells reside. Current cancer therapies aiming on tumor regression may target and kill differentiated tumor cells while sparing the rare cancer stem cell population. Cancer stem cell research is likely to provide a better insight into the mechanisms of tumor resistance to chemotherapy and might therefore lead to new therapeutic targets and better anticancer strategies. This review will summarize the investigated surface markers of haematological and solid tumors' stem cells since the appropriate identification and isolation of this particular subpopulation of tumor cells will be essential for developing more effective cancer treatments. © 2008 Springer Netherlands.