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How Cancer Cells Start to Spread

University of Manchester researchers have discovered a key process that may be involved in the spread of cancer by studying the growth of human embryonic stem cells.

Supported by an AICR grant, Dr Chris Ward and his team used these cells to investigate how tumour cells are able to migrate to other parts of the body, where they can form secondary tumours.   They studied a crucial biochemical change that makes cancer cells able to start moving and spread into other tissues.

Normal cells, as well as early cancer cells, are called epithelial cells because they bind tightly to each other forming stable layers of tissue. However, as a tumour becomes more advanced some of the cells change to become ‘mesenchymal’. Mesenchymal cells do not bind to each other, forming more disorganised tissues in which the cells can move around. Since this crucial change – known as the epithelial-mesenchymal transition – was first observed in the early embryo, Dr Ward theorised that embryonic stem cells might undergo a similar process.

When they examined these cells, they found that the protein E-cadherin stopped them from migrating during normal growth. They also found that, as well as helping cells stick together, E-cadherin also blocked the action of another protein known to increase the movement of cells. This important dual function of E-cadherin opens up the potential for new targets to prevent tumour cells from spreading.

Dr Ward said: “We have shown that these cells spontaneously change in a manner that is remarkably similar to the epithelial-mesenchymal transition. They lose the proteins that cells use to bind to each other and have other protein alterations that are characteristic of spreading cancer cells.  Since embryonic stem cells can be grown in the laboratory, where they keep the characteristics of the cells in the early embryo, they can be studied in detail. By studying these cells we have already identified a novel component of this transition process. We expect the use of stem cells will lead to the identification of other unknown factors involved in cancer cell spread, hopefully leading to new avenues for cancer therapy.”

Previously, it has not been possible to study this crucial transition in patients since this would involve invasive techniques that may interfere with any treatment of the disease. Where excised tumour cells have been used, it is difficult to know if the cells were from the right area – i.e. the growing part of the tumour. The team’s discovery that it happens spontaneously in ES cells means that it can be studied much more easily in the laboratory.

“Understanding how cancer cells start to spread is tremendously important for cancer research,” said Dr Ward, “It is the ability of tumours to invade into other tissues and spread around the body that makes them so dangerous. Finding out more about the mechanism that controls the spread of cancer cells will help us find new treatments that can prevent tumours spreading and make them essentially harmless.”

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