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Bowel stem cells

Bowel tissue, showing tumours developing. Credit: N. Barker

Stem cells are a hot topic in cancer.  In recent years we’ve seen the rise of the “cancer stem cell” concept – the idea that many cancers are caused by a small group of immortal stem cells. These produce ‘bulk tumour cells’, which can be killed off by treatments such as chemotherapy, but the stem cells themselves are resistant to treatment.

The cancer stem cell theory provides a neat explanation of why cancers can come back after many years, but the idea is controversial.  Some researchers think that all cancers boil down to stem cells, while others maintain that only a proportion of cancers are fuelled by these cells.

There’s certainly good evidence for the involvement of cancer stem cells in leukaemia, and scientists have suggested that stem cells drive many other types of cancer, including breast, skin and prostate.

US scientists writing recently in the journal Nature used new techniques to show that melanoma skin cancer – a disease that had previously been thought to be driven by stem cells – defied the theory, ramping up the controversy.

But this week’s Nature carries a report from Cancer Research UK scientists in Scotland and Cardiff, working with researchers in the Netherlands, showing that stem cells are at the root of bowel cancer.

A knockout blow
Dr Owen Sansom from the Beatson Institute for Cancer Research and his colleagues carried out a neat experiment to show that bowel stem cells could ‘go rogue’ and fuel cancers.

Due to everyday wear and tear, the cells that line our bowels are constantly being replaced.  New cells are produced from stem cells deep within cavities (crypts) in the bowel wall, in a complex biological ‘production line’.  This process is tightly controlled – too few new cells would lead to the bowel lining breaking down.  But over-production of cells can lead to cancer.

In their experiments, Sansom and his team used genetic engineering techniques to ‘knock out’ the activity of a crucial gene called APC in healthy bowel stem cells in the small bowel of mice. They discovered that tumours developed within a few days, which aggressively spread within a few weeks.

Next, the scientists knocked out APC in normal bowel lining cells, and found that tumours also developed, but much less readily or frequently than those from the stem cells.

The results suggest that the stem cells are much more likely to give rise to cancer that the lining cells.  The scientists also found that the stem cell-derived cancers produced ‘bulk’ cancer cells similar to bowel lining cells, supporting the classic cancer stem cell concept.

So we now know that stem cells are likely to be the fuel for bowel cancers – at least in mice.  But does it hold true for humans too?

Similarities and differences
Obviously, it’s virtually impossible to do genetic engineering experiments directly in humans. But we do know that the mouse system the team was using is a very good model for the development of human bowel cancer.

There’s one key difference though.  Experiments with mice have shown that their bowel cells only need one or two major gene faults to push them down the cancer path, whereas human bowel cells need several more.  But these results suggest that stem cells are ‘on the brink’, and need only a relatively small genetic push – whether that’s one fault or several – compared with other cells in the bowel.

More experiments need to be done before we know for sure whether stem cells play a vital role in human bowel cancer.  For now, these results are a promising step in the right direction – and a confirmation that the stem cell theory may well hold true for at least one type of cancer.

If we can understand more about the molecular pathways that control cancer, we can start to design new, more effective ways to prevent and treat the disease.

Click on the player below to hear Dr Sansom talking about his work in a short audio clip:

Audio clip: Adobe Flash Player (version 9 or above) is required to play this audio clip. Download the latest version here. You also need to have JavaScript enabled in your browser.

Link to download (1.5Mb, 3min10)

Kat

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Comments

Mike March 6, 2009

I would be interested to know which chemo D.Casemore had to remove multi secondaries as I have had two secondary events, both removed by surgery as the chemo didn’t seem to work.

D Casemore February 10, 2009

I had ca. colon removed a year ago – picked up through +ve occult blood test (I seemed generally in good health at the time). Chemo was successful in removing multiple secondaries in the liver; CEA is ~1.

My delight in the outcome is now somewhat tempered by this news although I’d rather know than not. Is there any info on the frequency of recurrence?

Valerie Thomson February 10, 2009

I had bowel cancer three and a half years ago aged fifty and find the news that in England the test kits will only be available to people aged between 60 and 69 very unfair. Should we all move to Scotland? I have to agree with Carol Gill that it does feel like bowel cancer is overshadowed by breast cancer.

Carol Gill February 9, 2009

I have had bowel cancer and know it may come back. It’s good to hear of research into causes of bowel cancer. Sometimes it seems to be very overshadowed by breast cancer.

Kat February 6, 2009

Phyllis, according to that page on CancerHelp UK, Northern Ireland should be rolling out their bowel sreening programme in 2009. Sorry for the omission!
Kat

phyllis mcauley February 6, 2009

hi kat, im just reading about the national bowel screening programe, you mentioned england, scotland and that wales had only just started to give out kits, but you didnt say anything about northern ireland. do you know when the kits will be avalable here?
regards phyllis.

Kat February 6, 2009

The national bowel screening programme is currently being rolled out across the UK. When it gets to your area, you will receive a package in the post containing the test kit. In England, the test should be going to everyone ages 60 -69, and you can request a kit if you are over 70 (in Scotland, kits are going to all aged 50-74, and in Wales they have only just started).

There’s lots more information about the test on our CancerHelp UK website here:
http://cancerhelp.cancerresearchuk.org/type/bowel-cancer/about/screening/about-bowel-cancer-screening

Kat

J C Hutchinson February 6, 2009

We have heard that there is a national campaign to issue bowel cancer test kits to anyone who is over the age of 55. Our GP surgery does not seem to know of this.
Can you please advise and give me details,as my wife
and I are both over 65, and would be very interested.

chris Woollams February 6, 2009

So it seems more and more that Scottish embryologist Dr Beard was right way back in in 1906. He was quite clear that one route to cancer was stem cells staying as trophoblasts under the influence of oestrogen. He was pilloried. His other theory was that pancreatic enzymes could help turn the stem cell into a normal cell and thus help stop some cancers; just as Dr Gonzalez in New York, with the FDA looking over his shoulder, seems to be showing. Such a shame we have ignored research for 102 years really. Think of all the wasted research monies, if only we had listened. You can find out all about this at http://www.canceractive.com

Catriona Hamilton February 5, 2009

Very interesting.
Our eldest son who is an intestinal transplantee suffered from PTLD Post Transplant Lymphoproliferative Disorder a form of b-cell lymphoma in his duodenum,he was sucessfuly treated with monoclonal antibody therapy but another treatment at the time was T-cell therapy.
My mother was taken from us due to bowel cancer.
Keep up your amazing work!

Owen Sansom January 26, 2009

Well done, a really nice summary of our work.