There has been much controversy over the compelling idea of cancer stem cells - a small subset of "master cells" that drives the growth and development of a patient's cancer. Now an international team of scientists that tracked the gene mutations driving cancer in patients with a rare blood condition that frequently develops into acute myeloid leukemia, says it has proved conclusively that cancer stem cells exist.
Led by the University of Oxford in the UK and the Karolinska Institutet in Sweden, the scientists report their findings in the journal Cancer Cell. They describe how they tracked the genes of malignant cells in the bone marrow of patients with myelodysplastic syndrome (MDS) and followed them over time.
MDS is a rare condition where the bone marrow does not make enough healthy blood cells and there are abnormal precursor or "blast" cells in the blood and bone marrow. The condition causes a drop in healthy blood cells and frequently develops into acute myeloid leukemia, the most common type of acute leukemia in adults.
Cancer stem cells could be key to eradication of cancer
Stem cells are master cells that give rise to all the 200 or more different types of cell in the body to make normal tissue and organs. For some time, scientists have been seized by the idea that like normal tissue, cancer is also driven by stem cells that replenish themselves and give rise to the other types of cancer cells.
The concept that cancer is driven by stem cells that replenish themselves is important because it suggests cancer could be eradicated by eliminating cancer stem cells.
The concept is important because it suggests cancer could be eliminated by eliminating cancer stem cells. Targeting cancer stem cells would also mean the remaining cancer cells could not sustain themselves.
First author Dr. Petter Woll of Oxford's MRC Weatherall Institute for Molecular Medicine, likens it to "having dandelions in your lawn. You can pull out as many as you want, but if you don't get the roots they'll come back."
Some studies have already pointed to the possibility of cancer stem cells in a number of human cancers. For example, in March 2013, scientists reporting in Nature suggested cancer of the ovaries may arise from stem-like cells, and in three papers published a year earlier in the same journal, investigators described how cancer in the brain, skin and gut may have its own stem cells that drive the regrowth of tumors.
However, study leader Sten Eirik W. Jacobsen, a professor at Oxford's MRC Molecular Haematology Unit and also of the Weatherall Institute, says many previous studies have remained controversial because the lab tests used to identify cancer stem cells have since been considered unreliable, and do not show the "real situation" inside an intact tumor in a live patient.
Gene-tracking found which cells give rise to cancer-driving mutations
Prof. Jacobsen, who also holds a guest professorship at the Karolinska Institutet, says:
"In our studies we avoided the problem of unreliable lab tests by tracking the origin and development of cancer-driving mutations in MDS patients."
Using gene tracking tools, he and his colleagues found which cells gave rise to cancer-driving mutations that propagated into other cancer cells.
They also showed that a distinct and rare sub-group of MDS cells, and no other malignant MDS cells, were capable of driving the tumor.
This rare subgroup of MDS cells bore all the hallmarks of cancer stem cells: they sat at the top of a hierarchy of MDS cells, they appeared able to sustain themselves, to replenish the other MDS cancer cells, and give rise to all the stable DNA changes and mutations that drive the disease.
Dr. Woll says these features offer "conclusive evidence for the existence of cancer stem cells in myelodysplastic syndromes."
"We have identified a subset of cancer cells, shown that these rare cells are invariably the cells in which the cancer originates, and also are the only cancer-propagating cells in the patients," he adds.
'Vitally important step' to eliminating cancer at the root
The findings are "a vitally important step," explains Dr. Woll, because they suggest, "if you want to cure patients, you would need to target and remove these cells at the root of the cancer - but that would be sufficient, that would do it."
While the findings are not sufficient to offer patients new treatments today, they do pave the way for developing more effective therapies that target specific stem cells to eliminate cancer, he adds.
Among the things they need to investigate further is what makes these cancer stem cells unique, and what are the biological pathways that are specifically dysregulated in cancer stem cells. Those could then be the target of new drugs, says Dr. Woll.
He also cautions that their study only looked at cancer stem cells in MDS, and that the "identity, number and function of stem cells in other cancers are likely to differ from that of MDS."
Funds from the National Institute for Health Research Oxford Biomedical Research Centre, the Leukemia and Lymphoma Society, Leukaemia and Lymphoma Research, and the Knut and Alice Wallenberg Foundation, helped finance the study.
Written by Catharine Paddock PhD