Researcher: Dr Matthew Brookes, University of Birmingham  

Project Title: A Role for Iron Transport Proteins in Gastrointestinal Adenocarcinoma

Nycomed/Core 1 Year PhD Extension Award - completed December 2007

Iron is essential in general health and well being. However, too much iron in your body can have undesirable effects. Excess iron has been associated with a number of cancers in the gastrointestinal tract, including colon and oesophageal cancer. Oesophageal cancer is increasingly common in the UK and is associated with a poor prognosis (with a 5-year survival of less than 10%). Barrett’s oesophagus is a pre-cancerous condition associated with oesophageal cancer. This condition is characterised by a change in the lining of the oesophagus.

However to date how iron influences disease progression at the molecular level is not understood.

The research team has shown that iron levels are altered in Barrett’s oesophagus, oesophageal cancer and colon cancer, leading to increased iron transport to the cells. The aim of the research was to investigate these changes further, by using iron to stimulate oesophageal cancer cells to determine the changes in cellular behaviour, in particular to see if the tumour becomes more aggressive. Once we have determined these changes, we intend to modify the levels of the iron transporter proteins to see if we can reverse these effects.

If these experiments are successful, we hope that modifying the levels of iron transporters may become a potential therapeutic target for treating cancer of the gastrointestinal tract.

This is Dr Brooke’s final report:

Results of the Research

1. The results of this study have demonstrated that the proteins involved in importing iron into the malignant cells are increased in both colorectal and oesophageal cancer. This is associated with changes in the function of the iron exporter proteins, suggesting that the cells can rapidly increase their iron content in both of these tumours. This was confirmed in this study where we found that the iron level within oesophageal and colorectal cancer cells was much higher than the level found in normal cells.

2. The effects of increased iron levels in both of these cancers was then determined. The results suggested that there was an increase in the ability of both colorectal and oesophageal cancers cells to grow when the iron levels in these cells was increased. This increase in cellular iron in these two cancers also appears to increase the chances of the cells to spread and invade other organs. These results therefore appear to confirm for the
first time that iron is important in the progression and development of both colorectal and oesophageal cancer.

What are the implications for future prevention, treatment or cure?

These results suggest that iron appears to be important in both oesophageal and in colorectal cancer. Thus patients who have might have pre-cancerous lesions such as colorectal polyps or Barrett’s oesophagus might be responsive to the use of drugs (iron chelators) which block dietary iron absorption, and might help to prevent the progression of these conditions.

What future research might emanate from your work?

I intend to investigate this work further by looking at the effects of iron rich diets in animal models of these diseases, and the effects of iron chelation in these same models.