Understanding how cancer cells grow

Most tissues in the human body are maintained by stem cells – master builders and repairers that replenish different types of cells when needed. The unique properties of stem cells are of great interest to scientists investigating the possibility of regenerating and repairing human tissues. But stem cells have also come under close scrutiny in relation to cancer, since the ability to self-renew is a characteristic of tumours. Research into cancer stem cells is offering new insight into how cancer cells grow and how some tumours relapse even following powerful therapy.

Cambridge has a very active stem cell community, recognised as a centre of excellence by the Wellcome Trust (WT) and the Medical Research Council (MRC). A major research theme within this community is the Cancer Stem Cell Programme at the MRC Centre for Stem Cell Biology and Regenerative Medicine. Professor Fiona Watt, who directs the Programme, explained why cancer stem cells are so interesting: ‘Pathologists have known for centuries that within a single tumour there can be cells that differ in maturity. It is now becoming clear that this heterogeneity reflects, at least in part, the existence of cancer stem cells and their offspring, and that these cells play a crucial role in the life history of cancer. Eradicating these master builders would strike at the heart of the tumour.’

Cancer stem cells

The Cancer Stem Cell Programme brings together clinicians and scientists with expertise in haematological, epithelial and brain cancers.

One of the best-studied adult stem cell systems is the process by which the many different cell types found in blood are constantly replenished. Professor Tony Green and Dr Brian Huntly in the Department of Haematology are using this process as a paradigm for understanding leukaemias: ‘We are especially interested in the molecular rewiring that underlies the change from a normal cell to a cancerous stem cell,’ explained Professor Green. A recent success has been the discovery of a new molecular mechanism for leukaemia.

To identify cancer stem cells and their complex interactions, researchers frequently develop biological models of cancer. Dr Stephen Goldie in Professor Watt’s lab, in collaboration with clinicians at Cambridge University Hospitals NHS Foundation Trust, is investigating cancer stem cells in human head and neck tumours by creating models that recapitulate the original human tumour. ‘Interactions between the tumour and its environment are being tracked by state-of-the-art imaging technology to establish which cells are responsible for making the tumours and what can be done to make the tumour shrink and stop spreading,’ explained Dr Goldie.

Scientists from the Centre for Brain Repair in the Department of Clinical Neurosciences and the WT Centre for Stem Cell Research are investigating stem cells in brain cancer. ‘Brain cancer accounts for a disproportionate number of cancer deaths and new treatments are urgently required,’ explained Dr Colin Watts, Consultant Neurosurgeon, from the Centre for Brain Repair. ‘These tumours contain stem-like cells that are resistant to current treatments. Work in the Centre aims to understand the mechanisms underlying this resistance and to develop ways of killing these cells.’

Driving new treatments

The current thinking is that cancer stem cells constitute a minority of the cells within a tumour and, although they are capable of dividing continually, they may do so relatively slowly. Most therapies are targeted towards rapidly dividing cells, which might kill the bulk of the tumour but not the cancer stem cells. Understanding more about cancer stem cells is therefore crucial, as Professor Watt explained: ‘Future treatments that are specific for cancer stem cells will not only be more effective in treating the disease, but will also incur less collateral damage to the patient’s normal tissues.’

For more information, please contact Professor Fiona Watt (fiona.watt@cancer.org.uk), the Herchel Smith Professor of Medical Genetics, at the Wellcome Trust-MRC Stem Cell Institute and the Cancer Research UK Cambridge Research Institute/Li Ka Shing Centre.