Contagious cancers switch their batteries

By Ed Yong | January 20, 2011 2:02 pm

Parasites come in many forms, including bacteria, viruses, fungi, worms and more. But a very different sort of parasite is infecting dogs around the world. It’s a contagious cancer.

CTVT, or canine transmissible veneral tumour, is a cancer that has evolved into an independent global parasite. Most cancers (including those that affect humans) aren’t contagious. Although some infectious diseases can lead to cancer, you cannot actually catch a tumour from someone who has one. But CTVT is an exception – the cancer cells themselves can spread from dog to dog, through sex or close contact.

A Russian veterinarian called Mstislav Novinsky first discovered the disease in the 1870s, but it took 130 years for others to discover its true nature. In 2006, Robin Weiss and Claudio Murgia from University College London compared CTVT samples from 40 dogs across the world. All of them carried distinctive genetic markers that set them apart from the cells of their host dogs. They all had a common ancestor – an ancient tumour that escaped from its original host and took the world by storm.

CTVT is one of two types of contagious cancer. The other plagues Tasmanian devils and might drive them to extinction. While this second type is confined to Tasmania, CTVT has become a global success story. Hopping across continents on the bodies of dogs, this cancer cell has become an immortal parasite. The ones that Novinski studied in the 1870s were probably largely identical to the ones that Weiss and Murgia looked at 130 years later.

But this immortality comes at a price. The contagious cancer sometimes gets a glitch in its power supply, and it has to swap to a new set of batteries. Claire Rebbeck from Imperial College London has found that as the cells spread, they can pick up small structures called mitochondria. These are the batteries that provide our cells with energy, and the tumours can replace their set by raiding their hosts.

Mitochondria have their own small genome. Rebbeck looked at these little sets of DNA in 37 CTVT samples from four continents. Like Weiss and Murgia before her, she found that the cancer cells had mitochondrial DNA that was very different to that of their hosts. This shows, once again, that the tumours had spread from dog to dog, rather than rising up independently in each animal.

But Rebbeck also found that her mitochondrial sequences were far more diverse than she expected. When she drew a family tree of their evolutionary relationships, she found that the samples fell into two big closely related groups, with three black sheep that sat on their own (see the red boxes below). And when she did the same thing using DNA from the tumours’ main genomes, she got a different pattern.

This strongly suggests that the contagious cancers are occasionally picking up mitochondria from their hosts. They have done this many times, ever since the original cancer cell broke free for a life of independence. This probably happened around 10,000 years ago, although the ancestor of today’s tumours probably arose just 250 to 2,500 years old. That still makes CTVT the oldest lineage of mammal cells still around.

Why do the cancer cells need new mitochondria? Rebbeck thinks that they burn a lot of energy, and their DNA has a habit of changing quickly. Many of these changes will be harmful. If the cancer cells were confined to the same place, the weaker ones would eventually be weeded out. But that’s not the case – they can go on the move, taking their increasingly hobbled mitochondria with them.  The solution: steal fresh mitochondria from a new host. CTVT is well placed to do this, because it evolved from an immune cell called a histiocyte, which can swallow things around it.

This story is about more than just a fascinating contagious cancer. It also reminds us about the importance of mitochondria to animal cells, whether normal or cancerous. Last year, I wrote about a paper by Nick Lane and Bill Martin, two scientists who think that mitochondria were the key to the evolution of complex cells.

Mitochondria are the remnants of bacteria that were once engulfed by an ancient cell. That’s why they have their own genome. By forming this partnership, the swallowing cell gained access to unparalleled supplies of energy, turning it from a sleek sportscar into a gas-guzzling monster truck. That, in turn, allowed it to escape the shackles of simplicity by developing more genes and experimenting with more types of genes. Every animal, plant, fungus and alga on the planet rose from the results of this old partnership. And so do contagious cancers.

Reference: Rebbeck, Leroi & Burt. 2011. Mitochondrial Capture by a Transmissible Cancer. Science http://dx.doi.org/10.1126/science.1197696

More on contagious cancers:

Comments (12)

  1. Old Geezer

    So…what keeps this from crossing into humans? I’m thinking Mad Cow and AIDS. These did not rely on sexual contact to cross the barrier. Could it cross as a result of improperly cooked meat in those societies that have dog as a diet staple?

  2. Mike B

    Doubt it would move as easily as most pathogens; you’re dealing with a larger and more fragile cell (hence the need for “switching batteries” described here most likely). That would be far more sensitive to cooking than an inactive viral particle or prion. It would also look more foreign to our immune system than to a dog’s I’d expect, and it’s questionable whether its tricks to evade immune response would work on us. So, while I suppose it’s technically possible these things could jump the species gap, they have a lot more against them managing it than most pathogens I’d think.

  3. Dunbar

    What would keep it from crossing over to humans is the fact that CTVT is adapted to dogs and to evading canine immune systems. If you were to graft a CTVT to a human, the most likely scenario would be an immediate rejection by your immune system. It’s the same sort of phenomenon that frustrates xeno-transplants of animal organs into humans. Also, an observation: I doubt societies that eat dogs (which doesn’t really happen that often, at least in China) would accept eating a cancer-ridden dog any more than they would eat flu-infected chickens or scrapie-infected sheep or foot-and-mouth infected cows. So the answer to your question is, no.

    On HIV, it evolved from a simian virus called SIV. Since apes and such are our closest living relatives, it isn’t too hard to imagine how a virus that can infect them might be able to somewhat infect us and then successively evolve to be a human-specific pathogen by adaptation.

    “Mad cow” isn’t really contagious amongst humans anyway, because it is incredibly unlikely for one human to eat another human that ate contaminated beef, at least nowadays. There have been human to human transmissions of human prions in societies that practised cannibalism (look up Kuru in Wikipedia).

  4. Nathan Myers

    There’s no reason to think, is there, that none of the myriad cancers that plague humans are of this sort. Has anybody really looked? How would you go about that?

    I don’t understand how the cancer could have originated both 10,000 years and 2500 years ago.

  5. Dunbar

    To see if any cancer is contagious, I’d imagine they would apply the same epidemiological principles with regard to other infectious microbes, like identifying patient zero and such. To my mind, one human can get a cancer from another human, like if the former got a bone marrow transplant from the leukemia-afflicted latter. Of course, this doesn’t mean that the cancer is contagious because people normally don’t go around giving each other bone marrow transplants; people do, however, go about bumping uglies and/or fighting, so if ever a human transmissible cancer is found, we’d probably figure pretty quickly how it is transmitted.

    The cancer originated 10 000 years ago, but the current strain infecting dogs today branched out from its cousins around 250-2500 years ago. That’s how I read the statement.

  6. Trond Engen

    Nathan: I don’t understand how the cancer could have originated both 10,000 years and 2500 years ago.

    Act of Independence: 10000 years ago.
    The last common ancestor of current cells: 2500 years ago.

    I.e., only one of the doubtless many branches stemming from splits between 10000 and 2500 years ago has survived.

  7. JGB

    It’s slightly different, but in many ways the same phenomena. The human HeLa cell line derived from Henrietta Lacks, has evolved to the point of being a successful single celled organism within the last 60 years, and it now somewhat routinely is found as a contaminate in labs.

  8. This is really cool. And I love the evolutionary implications. However, aren’t our (human’s) mitochondrial DNA exceedingly similar from individual to individual? I’ve always heard the mitochondrial DNA as described as “more-ancient”. If this is true, then there was likely something very different about the earliest cells engulfed mitochondria than the cancer cells described in Ed’s post. Or, possibly, if the process/hunger for new energy was the same, there must have been a ver stable individual cell-mitochondria composite that found some sort of equilibrium point allowing the individual to develop and evolve into more complex things.

  9. @Dunbar, Nathan and others – There’s no evidence to date of a similar thing going on in human cancers and bear in mind that these are some of the most thoroughly researched diseases around. However, when I last wrote about this, I mentioned that the best place to look for such cases would be in people with weaker immune systems including transplant patients and those with HIV.

  10. You said “Most cancers (including those that affect humans) aren’t contagious”. Out of curiosity, are there any cancers that are directly contagious? I understand some cancers that are related to infection can be “contagious” because the virus or bacteria are contagious, but are there any analogs to CTVT in humans?

  11. Casey – I had to say most to account for CTVT and the Tasmanian devil facial tumour. As far as we know, these are the only two directly contagious cancers. There aren’t any that affect humans.

  12. gcochran

    Something similar was observed in Syrian hamsters, once upon a time. Note that CTVT is not that virulent, which is not surprising, considering that there is probably a payoff in allowing long host survival. Along that line, cell line infections like this don’t have to act like a cancer at all: they could cause a chronic illness, or even be fairly harmless.

    Some might practice host manipulation: they would have a good start, able (with a mutation or two) to manufacture all kinds of signaling molecules.

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