Cancer is caused by abnormalities in genes, which induce the cells to divide uncontrollably, or to escape death and the result of this, in solid tumours, is that a tumour mass (a lump or swelling) is formed. With time more genetic changes occur and these allow the tumour cells to spread to other parts of the body (metastasis), sometimes resulting in death.

It is now thought that these genetic changes occur before a cell acquires their full functional potential (differentiates) at which time they stop dividing, so that a bone tumour, for example, will not be initiated by one of the cells already functioning as bone but instead by a cell that has not yet differentiated - a stem cell. A stem cell population is present in many adult tissues, serving to replenish cell numbers after differentiated cells die or the tissue has been damaged. Normally there are stringent controls on when a stem cell is allowed to divide, but in cancer this mechanism is disrupted.

The idea that cancers derive from and are maintained by cancer stem cells is not a new one but it is only now that good evidence is being generated to support this concept. The cancer stem cell has a high proliferative ability but also the potential to self-renew, meaning that it can divide to produce both differentiated tumour cells and more cancer stem cells. It is this self-renewal potential that is the unique property of stem cells, and that ultimately gives rise to the varied population of cells seen in cancer, with a minority of cancer stem cells present.

Cancer stem cells have recently been identified and isolated in breast, colon and brain tumours, as well as in leukemias, with experiments showing that as few as 100 cancer stem cells are sufficient to give rise to a new cancer whereas, once the stem cell population is removed, even 100,000 of the remaining tumour cells are unable to do the same. This cancer stem cell population is also thought to be the reason why many chemotherapies appear to be effective at first, causing a large decrease in tumour size as a result of killing most tumour cells, but ultimately result in the regeneration of the tumour, as the cancer stem cells have a special mechanism of resistance to chemotherapy.

As a multi-disciplinary research team, comprising scientists and medical experts, we have knowledge in both stem cells and cancer, in particular mesenchymal tumours, including osteosarcomas, to undertake this project. Using our knowledge of stem cell biology and surface proteins (markers) produced by mesenchymal stem cells, in particular, we aim to identify and isolate the stem cell population in osteosarcomas. First, we will determine the proportion of cells expressing these stem cell markers in over 100 osteosarcomas and whether this population is resistant to chemotherapy. We will then isolate these cells and test for their ability to regenerate the original tumour at low numbers and compare this to the remaining cancer cell population. The regeneration of the original tumour will show both the proliferative and the self-renewal potential of the cancer stem cells. In addition, using already established models, we will test for the ability of the cancer stem cells to differentiate into bone, cartilage and other cell types and will also investigate the mechanisms that maintain these cells as stem cells that could be targeted by therapy.

The identification and characterisation of the cancer stem cell population in Osteosarcomas is a key step towards understanding this cancer and therefore towards finding a cure.

Professor Adrienne Flanagan, Royal National Orthopaedic Hospital, Middlesex