David and Goliath in the fight against prostate cancer: how a tiny protein could help tackle a deadly disease
24 March 2014
Prostate cancer kills over 10,000 men every year in the UK, which is why Prostate Cancer UK have launched Men United v Prostate Cancer; an army of scientists, doctors, nurses, fundraisers, celebrities, politicians and supporters all taking action on men’s health. Dr. Val Macaulay’s lab at the WIMM is part of this team, and here Dr. Tamara Aleksic, a senior scientist in the lab, describes new findings from the group that may help to develop new treatments for this terrifying disease.
Insulin growth factors (IGFs) are small proteins that circulate in the blood and help the body to grow and develop. Unfortunately, IGFs also help tumours to grow too, and it is known that men with high blood IGF levels are at greater risk of developing prostate cancer.
IGFs work by sticking to a protein called the type 1 IGF receptor (IGF-1R), which sits on the surface of cancer cells. When IGFs stick to IGF-1R, the IGF-1R protein gets switched on and sends messages to the cancer cell, telling it to grow and spread.
Our lab has shown that prostate cancers have more IGF-1R than the normal prostate (see image). It is also known that in many tumour types, including prostate cancer, patients whose cancers have lower amounts of IGF-1R also have smaller tumours and fewer secondary tumours (metastases). Thus, the IGF-1R is an attractive target for cancer therapy.
Standard cancer treatments including chemotherapy and radiotherapy try to kill tumour cells by directly damaging the cell’s DNA, but these treatments are often ineffective because cancers are particularly good at repairing the damage.
IGF-1R plays an important role in keeping cancer cells alive whilst they are attempting this repair process, so we thought that if we reduce the amount of IGF-1R, or use drugs to switch off IGF-1R within cancer cells, this would help chemo- and radio- therapies to be more effective. Indeed, we have now demonstrated that blocking IGF-1Rs in human prostate cancer cells makes the cells more vulnerable and easier to kill by radiotherapy.
Interestingly, we also found that when IGFs stick to the cell surface IGF-1R protein, the IGF-1R moves from the surface to the nucleus of the cell, where the DNA is found. This has never been seen before, and so we looked in other types of cancer – and found the same thing.
We found that patients with tumours that had a lot of the IGF-1R protein in the nucleus of the cell did not live as long as other patients with less of the protein, and so we think that the movement of the IGF-1R from the surface to the centre of the cell might make cancers behave more aggressively. We’re now working hard to find out why this happens.
If we can do this, we may be able to use drugs which target IGF-1R to make radiotherapy work more effectively, and improve the treatment of men with prostate cancer.
This research is funded by Prostate Cancer UK. Join the team at http://menunited.prostatecanceruk.org/
Post edited by Bryony Graham.