Cancer Stem Cells

  1. Normal stem cells obtain genetic defects that affect proliferation and/or differentiation.
  2. Uncontrolled proliferation can occur often with a block in the ability of the cells to differentiate. Treatment usually occurs here.
  3. Current treatments do not target stem cells so the cancer is able to regenerate.

Cancer stem cells have very similar properties to normal stem cells, that is they can self renew and differentiate to form mature cells. However, cancer stem cells have an additional property in that they can seed or regenerate new tumors. This means that within a tumor there is a very small population of stem-like cells that if isolated and allowed to regrow can form a tumor with identical properties to the one the cells were taken from.
 
The first cancer stem cells to be identified were leukemia-initiating cells (LIC) by John Dick and colleagues at the University of Toronto. They demonstrated that a rare population of cells from a patient that had acute myeloid leukemia were able to regenerate the leukemia when transplanted into mice with no immune system.  The rare cells were identifiable and could be isolated by specific proteins localised on their surface. Since these initial experiments, cancer stem cells have been identified in many other solid tumours including breast, brain, colon, and lung. Although the presence of cancer stem cells is well accepted there is still some debate as to the number of cancer stem cells within a given tumour. It is likely that the size of the stem cell population will be dependant upon the type of cancer and the degree to which it is homogeneous. This means in some tumours where the cells are very similar there may be more cancer stem cells, or cells able to regenerate the tumour, than in cancers where the cells making up the tumour are very different.
 
The discovery of cancer stem cells has major implications in the treatment of cancer. Most current treatments (chemotherapy and radiotherapy) target rapidly dividing cells that generally constitute the non-stem cell component of tumours, leaving the quiescent, transformed and very slow dividing stem cells to reinitiate the tumour. It is likely that effective cancer treatments will require strategies to target these aberrant stem cells.
 
This problem is being tackled in a number of different ways. Scientists are currently working to identify genetic changes that occur in normal stem cells that will affect their ability to proliferate or differentiate and that might contribute to them becoming cancer stem cells. Scientists are also developing high throughput assays to identify compounds that will kill the cancer stem cells.
 
References 

  1. Lapidot, T. et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367, 645-648 (1994).
  2. Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J. & Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100, 3983-3988 (2003).
  3. Singh, S.K. et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 63, 5821-5828 (2003).
  4. O'Brien, C.A., Pollett, A., Gallinger, S. & Dick, J.E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106-110 (2007).
  5. Eramo, A. et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15, 504-514 (2008).

 
Written by Louise Winteringham,
Western Australian Institute of Medical Research