National Geographic

Breast cells naturally transform into stem cells

Our bodies are rife with disappearing potential. We come from stem cells, which can give rise to all the diverse types of cells in the human body. They can produce neurons, muscle cells, skin cells and more. As their daughters become more and more specialised, they lose this ability and become stuck with a specific fate.

That’s the standard story – a one-way street of lost potential.

The story is wrong.

According to a provocative new study from Christine Chaffer at the Whitehead Institute for Biomedical Research, some specialised cells can spontaneously revert back to a stem-like state. The one-way street actually works two ways.

It’s a very surprising result. Until now, no one thought that these reversions were possible, and scientists have spent a lot of effort finding ways of artificially reprogramming specialised cells into a stem-like state. Now it turns out that cells can naturally do the same thing. It’s like suddenly discovering that the people you pass every day in the street have been secretly gaining superpowers under your nose.

All of this started with a simple observation. Chaffer was looking at a flask full of human breast cells and noticed that a small of them were floating, rather than stuck to the bottom. She says, “Normally when we see floating cells in tissue culture, they are dead or dying. However, in this case, I noticed that they maintained a healthy appearance.” Chaffer was intrigued, especially since she knew that this ability to survive in a free-floating environment was a trait that stem cells share.

“We suspected that these floating cells may contain a high proportion of a stem-like cell population,” says Chaffer, and she was right. Compared to other breast cells, these floaters were more likely to show three genetic markers that are telltale signs of stem cells. These include a weakly active CD24 gene, a missing ESA gene and, most of all, a strongly active CD44 gene.

These cells certainly behaved like stem cells. Even a single one could eventually produce clumps of breast gland tissue known as “mammospheres”, just like normal stem cells can. And when they were transplanted into mice, they could produce more complicated structures like milk ducts.

These “stemmy” cells seemed to come out of nowhere. Chaffer found that groups of cells with weakly active copies of CD44 would quickly develop daughters that had the strongly active version of the gene. This wasn’t because of any contamination – the high-CD44 cells actually grow more slowly than their low-CD44 counterparts, so they would normally be drowned out in a bustling culture. It became clear that the low-CD44 cells were actually turning into the high-CD44 ones.

This isn’t just something that happens in laboratory flask. Chaffer also found her special cells in fresh tissue samples, where they initially account for one in every 300 cells. Over time, other cells spontaneously turned into these stem-like ones.

This story would have been surprising enough, but Chaffer also found that breast cancer cells can turn into breast cancer stem cells. Cancer stem cells were discovered around 14 years ago, and they have since been found in many different types of tumour. The idea, and it’s still a controversial one, is that these elite cells produce most of the cancerous cells that make up a tumour. They could seed new tumours in different parts of the body, and regenerate tumours that have been mostly killed off by treatments, leading to recurrence.

When Chaffer transformed the floating breast cells into cancer cells, she found that the low-CD44 ones could transform into high-CD44 cancer stem cells around 2-5 times more quickly than their normal cousins. And the resulting tumours were more aggressive than normal.

This opens up a big can of worms. Several researchers are now trying to develop treatments that target cancer stem cells. The hope is that such drugs would seek and destroy the heart of tumours, robbing them of their ability to bounce back. But clearly, if normal breast cancer cells can turn into cancer stem cells, then this approach has a fatal flaw – the tumours could simply regenerate their heart.

If that seems pessimistic, Chaffer’s discovery heralds more optimistic news in other fields of medicine. Many scientists are furiously working on ways of reprogramming adult cells into stem-like ones, often by altering the cells at a genetic level. The resulting cells could be used to produce new tissues or even organs, all tailored to an individual patient’s genome.

There are risks to this approach, including (ironically enough) cancer, brought on by accidental changes to the wrong genes. But if Chaffer can work out how her cells were naturally regaining their “stemminess”, she could potentially find ways of duplicating the effect, without having to disrupt any genes. “If one can identify these particular population of cells in other tissues, they will hold great promise for the development of patient-specific adult stem cells for the treatment of degenerative diseases,” she says.

Reference: Chaffer, Brueckmann, Scheel, Kaestli, Wiggins, Rodrigues, Brooks, Reinhardt, Su, Polyak, Arendt, Kuperwasser, Bierie & Weinberg. 2011. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. PNAS http://dx.doi.org/10.1073/pnas.1102454108

Image by the JCB

Disclosure: In my day job, I work for a cancer charity called Cancer Research UK. The charity did not fund this study, but I have linked to its blog (which I occasionally write for) in a few instances above.

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There are 11 Comments. Add Yours.

  1. QoB
    April 12, 2011

    A new twist on the “I make milk. What’s your superpower?” tshirts!

  2. southlakesmom
    April 12, 2011

    “Over time, other cells from spontaneously turned into these stem-like ones.”

    I don’t understand this sentence. I’m not a scientist and don’t play one on TV, but I think this needs editing, not SCIENCE…

    Otherwise, as usual, interesting and provocative post, Ed.

  3. Fabicky
    April 12, 2011

    A great read, these ‘provocative’ findings by Chaffer are very exciting, please keep me updated.

  4. Nathan Myers
    April 12, 2011

    I don’t know why people keep saying that specialized cells are not known to de-differentiate back to stem cells. Robert Becker reported on it in the ’70s, and published in Nature and Science. He learned how to stimulate the change in vitro. Indeed, every time you break a bone, bone cells near the break de-differentiate, and then regenerate new bone, re-forming into all the various kinds of cells needed.

  5. Paul R Walsh
    April 13, 2011

    Hi Ed.
    Good choice of topic. This discovery has the potential for high impact.

    Editorially speaking, I agree with ‘southlakesmom': grammatically, there is a problem. Depending upon the level of detail you wish to communicate, the revision could vary. But, to impart the most general information, you could merely omit the word “from” in the sentence, “Over time, other cells from spontaneously turned into these stem-like ones.”

    Also, to maintain the high quality of your writings, please note the minor typo:
    ‘environemnt’
    should be
    ‘environment’

    Otherwise, I think the content is great. While I doubt that the OED will soon include an entry for ‘steminess’, your improvisational usage of the term epitomizes clear communication to the common man. Stephen J. Gould would surely nod his assent.

    just trying to be helpful,
    -paul

    P.S. I was surprised to find that ‘stemmy’ already appears in the OED (though not defined relative to stem cells.) Your usage should nonetheless be clear anyone who has heard of stem cells.

  6. Ash Dunne
    April 13, 2011

    Has anyone actually been able to find this paper yet? Tried the DOI link: invalid. Tried Pubmed, nothing. Tried PNAS search, nothing. I’d like to read the original paper!

  7. Ed Yong
    April 13, 2011
  8. Ash Dunne
    April 13, 2011

    Ed, thanks for this. Totally understand your frustration. Hope I haven’t added to it with previous comment!

  9. Anurag
    April 13, 2011

    If someone gets to know when this paper comes up online for access please post it here. Thanks.

  10. Michael Lerman
    April 13, 2011

    In 2007 I offered a hypothetical biochemical mechanism describing the phenomena concerning the origin and dynamics of TSC and CSC as follows:

    The von Hippel- Lindau disease TSG (VHL) may be involved in the creation of cancer stem cells (CSC). As adult tissue stem cells (TSC) will not tolerate mutations (the important tenet of the “immortal strand” hypothesis (1)) they can’t be precursors of CSC. These are created as follows: when an adult tissue stem cell divides it creates a stem cell (self-renewal) and dividing progenitor cells, which are destined to differentiate and eventually die; these dividing progenitor cells may accumulate cancer-causing mutations. To initiate cancer a mutated/transformed clone needs to block differentiation and convert to a stem cell status. Silencing VHL in these dividing “cancer” cells will induce the HIF transcriptional network leading to conversion into CSC, as HIF will induce the SC transcription machinery (2). Similarly, VHL silencing may create adult TSC from proliferating normal cells in developing/renewing tissues. Thus, VHL may be responsible for both fundamental events in biology.
    1. Cairns, J. Genetics 174: 1069-1072, 2006.
    2. Keith, B., Simon, M.C. Cell 129: 465-72, 2007.

  11. Cleidson Alves
    April 15, 2011

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