Cancer stem cells produce brain tumors
Mouse study demonstrates source of human cancer.
The cells that lie at the root of human brain tumours have been isolated, opening the door to treatments that stifle cancer at its source.
Researchers believe that tumours grow from a type of "cancer stem cell" that gives rise to other cancerous cells. Cancer stem cells appear to have some of the properties of stem cells, such as the potential to give rise to a larger population of cells, although they are not necessarily the same thing. For example, they may be differentiated cells that undergo a backwards step to take on some of these properties, although the pathway remains unclear.
Scientists have had little success tracking down these cells, because they are difficult to distinguish from surrounding cells.
To find the culprits underlying brain cancer, Sheila Singh and her co-workers at the Hospital for Sick Children, Toronto, Canada, turned to a protein called CD133, which has been found on the surface of other stem cells in the body. The group took tissue samples of brain tumours from children and adults and pulled out cells that were making the protein.
When the team injected 100 of these potential cancer stem cells into the brains of 19 mice, 16 of them sprouted brain tumours. The results, which the team reports in Nature1, support the idea that such cells are a subpopulation of brain cells that went awry, became cancer stem cells and gave rise to the human tumours.
Although the group have isolated cancer stem cells from human brains before2, this study is the first to show that these cells can recreate the disease in animals. This confirms that these cells are the ones that spawn tumours.
Moreover, the cancer stem cells grew into tumours that behaved similarly to those in the patients from which they came, resembling glioblastomas and medulloblastomas, for example. This suggests that mice tumours will be a good way to study the human disease.
Brain cancers are one of the most vicious and least understood forms of cancer because they are buried in the brain and are difficult to study or treat.
Scientists hope that the ability to pinpoint brain-cancer stem cells will lead to new ways to tackle them. "One question we ask is: 'Can we develop inhibitors to target these cancer stem cells specifically?'" says Jeffrey Rosen, who has studied these cell types at Baylor College of Medicine in Houston, Texas.
In future, researchers hope to classify the various cancer stem cells that spawn different forms of tumour. This might allow early diagnosis of tumour type and aid more accurate prognosis and treatment for each patient.
Scientists say they will probably go on to discover cancer stem cells acting in tumours of the pancreas, liver and other organs. But it remains unclear what switches a cell into a cancerous state. "How does a cell become a cancer stem cell? That's one of the toughest questions," says Peter Dirks, an author of the study.
- Singh S. K., et al. Nature, 432. 396 - 401 (2004).
- Singh S. K., et al. Cancer Res., 63. 5821 - 5828 (2003).