Research
FORCE continues to fund an on-going programme of Cancer Research in Exeter. This research is directed and supervised by a team of scientists and clinicians; all of whom are researchers with the Peninsula Medical School here in Exeter. Specifically, this includes Dr Jackie Whatmore, a cell biologist and Dr Paul Eggleton a biochemist, and also Dr Nick Gutowski a consultant neurologist and Mr Nigel Acheson, a consultant gynaecological oncologist who are both based at the Royal Devon and Exeter Healthcare Trust.
This exciting research currently involves two doctoral students, researching into two major areas.
An investigation into the mechanisms involved in the formation of brain metastases
Approximately one third of patients with lung cancer will develop a brain metastasis (i.e. secondary tumour) in the brain and these are an increasingly important cause of mortality. For these to form, some of the lung cancer cells from the primary tumour must detach and travel through the blood stream to the brain where the tumour cells need to cross the endothelial cells lining blood vessels and then invade the brain, coming into contact with astrocytes (the main supporting cells of the brain). It is generally recognized that the formation of a metastasis requires a complex sequence of events in which cells communicate with each other and the tumour cells induce changes in the surrounding tissue by secreting chemical messengers. However, the specific biological processes that allow metastases to form are largely unknown. Thus, this research involves investigating factors released from cultured lung tumour cells and examining their effect on both brain astrocytes and endothelial cells to see if the lung tumour cells induce changes in these cells. Excitingly, it appears that the lung tumour cells do secrete factors which influence both astrocytes and endothelial cells and the identity of these factors is currently being investigated. Clearly, if we can find out the mechanisms involved at the cellular level then hopefully we can design ways of reducing secondary tumour growth in the brain.
Investigations into the mechanisms involved in secondary spread of ovarian cancer
Ovarian cancer survival rates are much lower in women whose cancer has spread to other organs. Ovarian cancer is unusual in the way that it spreads because unlike most tumours the cancer cells are shed from the outside of the ovary and then simply attach to the outside of other organs within the abdomen. A major site for spread is the omentum (a sheet of fatty tissue in the abdomen). Ovarian cancer cells attach to the outside of the omentum and then invade the tissue and start to grow as secondary tumours. The endothelial cells lining the blood vessels in the omentum are important for this spread because as a tumour grows it releases chemical signals which activate the endothelial cells causing them to change and grow new blood vessels. This is essential to feed the growing secondary tumour. This project looks in detail at what chemical signals are released from ovarian cancer cells and the effects of these signals on endothelial cells isolated from the omentum. If we can find out exactly what these signals are and what they do at the cellular level then hopefully we can design ways of preventing new blood vessel, and thus secondary tumour growth, in the omentum.
We are uniquely placed to carry out this project in our laboratory because we are able to isolate fresh endothelial cells from the omentum for our experiments - an extremely difficult task. These cells are isolated from small pieces of tissue that are donated (with the full consent of the patients) during operations.
Both of these projects very successfully involve both basic scientists and consultant physicians who ensure that the research is not only scientifically rigourous but also importantly that it is clinically relevant.
The FORCE-funded research continues to be extremely productive. This research has been published internationally and widely presented at conferences both home and abroad. It has lead to considerable scientific collaboration, to the attraction of further external funding, and probably most importantly, through the research studentships funded by FORCE, provided vital training for cancer researchers of the future.
