Cells offer a cancer cure

SHONA Lang is peering through a microscope into a shallow plastic dish containing what looks, to the naked eye, like coloured jelly. She focuses, then lets me take a look.

Through the viewfinder I see what she has been looking at: tiny individual cells apparently floating before my eyes.

They are feeder cells, she says - and they play a vital, if unglamorous, role in the breakthrough just made by York scientists in the fight against prostate cancer.

The team at the Yorkshire Cancer Research Unit, based at the University of York, has discovered how to isolate the stem cells thought to cause prostate cancer. This breakthrough holds out hope of one day developing a new generation of treatments for a disease that claims the lives of 10,000 men every year in the UK alone.

The microscopy suite at the cancer research unit does not look at all remarkable.

It is a small, slightly claustrophobic room that is a harsh, clinical white under the bright overhead lights. A row of what look like fridges occupy most of one wall, and there are microscopes on a central bench area. It could almost be a small science lab in a secondary school - except that most schoolchildren aren't involved in the search for a cure for cancer.

It is here that much of the pioneering work being done by Professor Norman Maitland's stem cell research team is being carried out.

Stem cells are a bit like roots. They are the cells from which other cells in the human body grow. The York scientists who announced their breakthrough last week used a simple analogy to explain the significance of what they had done.

"Think of prostate cancer as a dandelion in a lawn," they said. "Pull the leaves off the

weed and the root still remains, allowing it to regenerate."

That has been the trouble with existing treatments for prostate cancer. They attack the ordinary cancer cells - the "leaves" - which make up the bulk of the cancer. But they leave behind the stem cells - the "root". The result? The cancers can grow back, often within two years of being treated.

The key to a successful treatment is to be able to attack the root of the cancer. Now that Prof Maitland's team has been able to isolate the cancer stem cells that make up that root - becoming the first team in the world to be able to do so for prostate cancer - it paves the way for a new generation of drugs which target those cells.

The stem cells may only make up one in every 1,000 of cancer cells, says Dr Anne Collins, who is leading the research: but because they are resistant to existing drug treatments they remain crucially important.

"We can get rid of 99 per cent of the prostate cancer using the therapies we've got, but not that one cell," Dr Collins said. "And it only takes one cell to grow back. We've got to design new therapies for that more robust cell type."

The search for those new therapies is likely to be a long one, but here in York, it is already beginning.

The technique developed by Dr Collins and her team to isolate cancer stem cells involves using antibodies to attach tiny magnetic beads to the stem cells' surface.

Patients who attend York Hospital for an operation to remove prostate tumours are asked if a sample of their tumour can be used for research.

Permission given, the tissue is brought back to the lab at the cancer research centre. Stem cells in the tumour are labelled using the magnetic beads, then isolated and grown in plastic dishes.

For research purposes, what is needed is a 'high density' culture involving many stem cells. It is not that easy. Because the cancer stem cells are so rare, researchers have to encourage them to grow, which is where Shona Lang's 'feeder' cells come in. They help to provide the nutrition that allows the stem cells to grow in the lab.

Ultimately, the idea is to use stem cells to make a 3-D 'model' of a human prostate using living cells in a test tube.

This 3-D model can then be used in the search for a new drug treatment. The key, says Dr Collins, is to find out in what ways cancer stem cells differ from normal stem cells in the prostate. That is what the team is working on now.

Thanks to the human genome project, we now know that the human genome is made up of between 30,000-40,000 different genes.

Given the sheer number of the genetic building blocks that go to make us up, the differences between a cancer stem cell and a normal stem cell are actually quite small.

Even so, the York scientists believe there are as many as 100 genes in a prostate cancer stem cell that are different to the genes found in a normal prostate stem cell.

The trick is to find which of those are responsible for causing the cancer stem cell to become cancerous. Find the genes that are responsible, and it may be possible to develop a drug to target them.

There are techniques for 'probing' the genes in cells, Dr Collins says. By 'knocking out' individual genes - or, alternatively, by stimulating particular genes so they become more active - it should be possible to see what effect that has on a cancer stem cell's ability to cause cancer-like symptoms in Shona Lang's 3-D model.

The approach potentially represents a way of developing drugs that target the harmful genes specifically, leaving healthy tissue unaffected.

New treatments are going to be some way off yet, however, Dr Collins says.

"At the moment we're really trying to find what to target," she said. "There are maybe 100 genes that are different in stem cells compared to normal cells. Which ones do you go for? We've got to really look at that."

Even once a potential drug has been developed, there will have to be extensive clinical trials, to ensure it works and does not have any harmful side effects.

Dr Collins is reluctant to be pressed on when a new drug treatment might be available, one that could wipe out the whole of a prostate tumour, not just the leaves.

The likelihood is, it is going to be ten to 15 years.

But, thanks to the York team, scientists are now beginning to look in the right places.

Stem cells and cancer

Scientists are beginning to believe cancer stem cells could be responsible for causing most cancers. Cancer stem cells had already been isolated for breast cancer, lung cancer, brain tumours and leukaemia before the York team isolated them in prostate cancer.

"It is likely that for most cancers it is the stem cells that cause the cancer," Dr Collins says.

Prostate cancer facts

*Cancer is the abnormal growth of cells in the body. Our bodies are made up of countless millions of cells, which are continually dividing and replacing each other. Sometimes something goes wrong, however, and the cells divide and grow too much. These can develop into lumpy bundles of cells called tumours.

*Prostate cancer occurs when cells in the prostate gland, which is part of the male reproductive system, start to divide and grow abnormally to produce tumours. Cells can also break free from these tumours and travel elsewhere in the body, beginning to start new tumours there.

*Every year, more than 30,000 men in the UK are diagnosed with the disease and 10,000 men die from it. Prostate cancer is now the most common cancer among men in the UK.

Yorkshire Cancer Research Unit

The unit, headed by Prof Norman Maitland, is based in the biology building at the University of York. It employs 16 researchers, plus four research students. Dr Collins leads a seven-strong team working on stem cell research.

The unit is funded mainly by an annual £300,000 grant from Yorkshire Cancer Research (YCR), the largest regional medical charity in the UK. It also receives a small amount of funding from the US Department of Defence, which gives money for cancer research.

Updated: 10:21 Wednesday, December 07, 2005