Scientists follow slime trail to trace cancer’s progression

Tracking the movement of primitive amoeba cells – known as slime moulds – as they form strange, slug-like structures is set to provide valuable information about how cancer develops.

Speaking at a conference in Palermo, Italy¹, a leading Cancer Research UK scientist will report that the crawling of the tiny creatures has much in common – on a molecular level – with the way that human cells move around within tissues.

Dr Inke Näthke has developed a system for using the organism to study a key gene involved in the development of cancer. And she believes that her research could bring valuable information about a number of other cancer genes as well.

Slime moulds – also called Dictyostelium – live among leaf litter and are not really slugs or moulds, but a social amoeba. They spend much of their time as a scattering of separate cells, but when short of food the amoebae gather together and enter the slug phase, in which they crawl about as a single organism and eventually form reproductive structures called fruiting bodies.

Dr Inke Näthke and her colleagues, working at the University of Dundee, have found that genes which control the mobility of human cells have similar functions in Dictyostelium – making the organism perfect for conducting experiments that would be too complex to carry out in human tissue.

Dr Näthke comments: “By studying social amoebae we were able to look at individual cells in relatively complex, tissue-like arrangements, which allowed us to explore some of the processes that go on during the development of cancer.

“The way Dictyostelium cells gather together has been studied in other contexts and we can use this knowledge to learn more about the disease. The organism is also very easy to grow and study and is a much cheaper option than using human cells.”

Dr Näthke and her colleagues have used Dictyostelium to study a gene called APC, which is known to play an important role in the development of certain cancers. People who inherit a faulty version of APC have a very high risk of developing bowel cancer and the gene is also faulty in many non-inherited forms of the disease.

Scientists think APC may be important for maintaining the organisation of tissues and helping cells to move around in a controlled manner. This is important in the bowel, where old and damaged cells are routinely discarded from the gut wall to prevent the build up of cells in a potentially cancer-causing environment.

Researchers gave amoebae small pieces of the APC protein molecule, made using the APC gene as a blueprint. One of these is similar to the pieces of APC found in cancer patients and works differently from the full-sized molecule, changing the way that cells behave.

The APC fragment seemed to alter the way that the amoeba cells crawled around in response to signals that usually attract them – as though the cells had lost the ability to respond to marching orders.

Dr Näthke believes the cells can understand the instructions but are physically unable to respond to them, supporting the notion that APC plays a role in cell mobility. Working out exactly how cells are affected by damaging APC will give scientists vital information about its function.

Dr Näthke adds: “We’ve set up a new system to study this key cancer gene – one which in a few years is likely to produce a wealth of information about how the disease develops. The system has been used in other biological studies for many years with a great deal of success.

“In a relatively short space of time, our studies have provided some interesting information about the role of this gene in cancer, and we think the organism will be useful for looking at a number of other genes as well.”

Cancer Research UK’s Chief Executive, Sir Paul Nurse, comments: “It’s difficult to study human diseases directly because the processes going on in our tissues are so complex, so scientists often use simple organisms as models instead.

“The discovery that we can use the slime mould as a model for some of the processes involved in human cancer is an important step forward and one that should help us to discover the function of a number of key cancer genes.”

ENDS

1. Dictyostelium 2002 Conference