The Loom

i-f26cf0968984bacc520d6817aa28c948-dog.jpgCan a tumor become a new form of life?

This is the freaky but serious question that arises from a new study in the journal Cell. Scientists from London and Chicago have studied a peculiar cancer that afflicts dogs, known as canine transmissible venereal tumor (CTVT) or Sticker’s sarcoma. It is a cancer of immune cells called histiocytes, and dogs typically develop grapefruit-sized tumors that disappear after a few months.

Some scientists have suggested that Sticker’s sarcoma can be transmitted from dog to dog, either by mating or by licking or touching a tumor. They noted that the tumor cells appeared to share a unique genetic marker. But skeptics noted that virus-like particles are often found in or around Sticker’s sarcoma. There’s lots of strong evidence that viruses can trigger cancers (such as cervical cancer), possibly as a strategy to spread themselves rapidly. Dogs that were struck with Sticker’s sarcoma could just be acquiring a cancer-causing virus from other dogs.

To sort out just what’s going on with this cancer, the authors of the Cell paper made a big survey of dogs with Sticker’s sarcoma, examining sick pooches from five continents. They analyzed the DNA from normal cells in the dogs, as well as the DNA from their tumors. They put the tumor cells in dishes to observe how they interacted with dog cells. The picture they got was remarkably detailed and–please allow me to use the word again–freaky.

All of the tumor cells shared the same genetic marker. A virus-like stretch of DNA, called a LINE-1 element, had been moved to a new location in the genome of all of the tumor cells. None of the non-tumor cells from the dogs had this LINE-1 element in this particular spot. Other genetic markers also revealed the tumor cells to be closely related to one another–and not closely related to the dogs in which they had been found.

At some point in the past, the tumor cells must have originated from normal cells. To figure out their heritage, the scientists drew up an evolutionary tree, based on comparisons of their DNA to that of dogs and wolves. The cancer cells descend either from a gray wolf (the closest relatives of dogs) or from one of the older East Asian breeds of domesticated dog. That ancestral cell probably existed in a dog or wolf that lived several centuries ago. The scientists came to this conclusion by studying the mutations that have arisen in the cancer cells. Based on estimates of how fast mammal cells mutate, the scientists estimate that the mutations arose over the past 2500 to 250 years ago. But since cancer cells tend to mutate faster than normal cells, they favor a date at the recent end of the range.

The scientists propose that several centuries ago, a histiocyte cell in a dog or a wolf turned cancerous. A mutation may have caused the cell to become abnormal–perhaps that LINE-1 element that marks Sticker’s sarcoma cells today. But natural selection would have favored other mutations as well that allowed its descendants to become more effective at growing into a tumor. During mating, some of the cancer cells managed to spread to the dog’s partner, where they could continue to proliferate.

Scientists have proposed parasitic cancers in a couple of other cases in the past. In the 1960s, there was a report of histiocyte tumors in a colony of hamsters; the scientists even argued that mosquitoes could spread the cancer from rodent to rodent. Earlier this year, scientists reported that Tasmanian devils were spreading a face tumor by biting each other. There are a couple differences between the Tasmanian devil cancer and the dog cancer. One is just a matter of methods; no one has yet looked for genetic markers in the Tasmanian devil cancer the way that scientists have in Sticker’s sarcoma.

But if the Tasmanian devil cancer proves to be a genuine infection, it must behave very differently than Sticker’s sarcoma. When Tasmanian devils get the face cancer, the tumor grows until it blocks their mouths and they die. Dogs, on the other hand, generally only develop a temporary tumor. Once the tumor clears, they acquire immunity from any further infection with the cancer. The scientists found that the Sticker sarcoma cells make very few of the surface proteins that vertebrates use to distinguish self from non-self. It appears that the tumor cells can avoid an all-out attack from the immune system. Instead, the immune system reins in the cancer cells, which can survive in the dogs even after their tumor disappears.

The parallel between these two kinds of cancer and different sorts of parasites is very striking. The Tasmanian devil cancer is a virulent parasite, like smallpox, that kills its hosts but can race quickly to new hosts. It’s a risky strategy for the cancer, because it may kill off its hosts faster than they can breed. Sticker’s sarcoma has taken a different route, establishing a more peaceful relationship with its hosts, like Toxoplasma does with us. As a result, it has managed to survive and spread for centuries. With a booming population of stray dogs to infect, it has a rosy future. “It represents the evolution of a cancer cell into a successful parasite of worldwide distribution.”

So here’s the big question which the authors don’t tackle head on: what is this thing? Is it a medieval Chinese dog that has found immortality? If so, then it resembles HeLa cells, a line of cancer cells isolated from a woman named Henrietta Lacks who died in 1951. After her death, scientists have propagated her cells, and in that time they have have adapted to their new ecological niche of Petri dishes, acquiring mutations that make it grow aggressively in the lab. One biologist even suggested that the cells should be consider a new species.

Sticker’s sarcoma has, without any intervention from scientists, become a cell line as well, and one that has survived far longer than HeLa cells have. It is distinct from its dog ancestors, and has acquired adaptations that allow it to manipulate its hosts for its own advantage as effectively as a virus or a blood fluke. A parasite evolved from a dog, perhaps.

One question the scientists do raise is how common such cancer parasites may be. Scientists have reported tumors that spread from transplanted organs, but these don’t have a way to sustain their spread for centuries. Still, between mating, biting, and otherwise making contact, vertebrates provide plenty of opportunities for cancers to spread. And it is striking that our immune systems–and the immune systems of other jawed vertebrates–are equipped to battle so strongly against foreign tissues. What for? It’s not as if Devonian-era sharks were giving each other liver transplants 400 million years ago. Perhaps, the scientists suggest, our ancestors had to fight against a different sort of tissue donation: cancer parasites.

Reference: Murgia et al.: “Clonal Origin and Evolution of a Transmissible Cancer.” Publishing in Cell 126, 477-487, August 11, 2006. DOI 10.1016/j.cell.2006.05.051

Update, 8/10 9:45 am: I unintentionally broke an embargo for this story. For some reason, I thought it lifted yesterday at noon, instead of today. I apologize to Cell for my error. (Thanks to commenter John Travis for pointing out my mistake.)

Comments

  1. #1 Alan Kellogg
    August 9, 2006

    I have heard that DFTA might be related to Stickler’s Sarcoma, having genetic material in common with it. Could be a case of viral or even bacterial transmission of genetic material between eukaryotic cells.

    I’m thinking that what we have with both lines is not just a case of speciation, but the appearance of at least one new phylum. Contradicting a cladistic truism that a higher order cannot arise from a lower.

    If it is a new phylum, then it would be the first entirely parasitic one, and may well mean fundamental changes in life overall.

  2. #2 Left_Wing_Fox
    August 9, 2006

    Whoa… now there’s a twist to the creationist canard. “You’ll never see a dog evolve into a cat!” Well, we might have just seen a dog evolve into a parasitic tumor creature. That’s X-files material right there.

    Cool stuff!

  3. #3 luca
    August 10, 2006

    woah!!! haven’t read the whole post yet, but it looks to me like… The Thing!!!

  4. #4 EJ
    August 10, 2006

    Left_Wing_Fox,

    It isn’t be difficult for YECs to incorporate evolution of a “higher” organism into a parasite into the narrative. I suspect some already have, along these lines— Before the fall: No parasites (or any disease), perfection in all life, no mutations. After the fall: Parasites of all sorts appear via mutations which “lose information”, whereby perfect organisms ultimately have descendents which lose their independence and can survive only as parasites.

    Of course there are problems with this story.

  5. #5 John Moore
    August 10, 2006

    It’s really just a transposon that’s hit the sweet spot in a cell’s genome that has made that host cell into an immortal cancerous cell line. Through positive selection via multiple dogs’ immune systems, variants have arisen that are easily transmitted and can evade the host’s immune system enough to continue proliferating without killing the host (or the dogs die of something else if they are strays before the sarcoma can kill them). But really, the cells are just a vehicle to proliferate that transposon. If the cells are killed and their DNA is taken up by other cells, that transposon has a chance to hop off and enter a new host cell. It’s win-win for the transposon regardless. The Tasmanian Devils are definitely in trouble with that infectious facial cancer. Only devils that run away or that are isolated from infected individuals will survive this current plague. Interesting perspective on molecular Darwinian selection affecting two different species in different ways. One will kill itself off and the other will likely spread over the globe from canine to canine.

  6. #6 djlactin
    August 10, 2006

    retrotransposon notwithstanding, this carcinogenic propagule can only be called a new life form that evolved instantaneously from another. we can only speculate how frequently similar events have happened. i doubt this is the only one. mimivirus, perhaps?

    we might have to revise that old ‘natura non facit saltum’ credo.

  7. #7 John Travis
    August 10, 2006

    Carl–I think you broke the embargo on this. It was supposed to be noon today (Thursday Aug 10) not Aug 9.
    –john

  8. #8 Carl Zimmer
    August 10, 2006

    John–You’re right; I realize now I screwed up. I’ve sent an apology to Cell. We’ll see how they react…

  9. #9 Robster
    August 10, 2006

    The crazy thing is that the tumor alledgedly managed to be transmitted in the first place. As often as animals get tumors, I guess that the chances are reasonable that one manages to develop a transmissible phenotype. I have to wonder if it arose in a low genetic variability population first.

  10. #10 luca
    August 11, 2006

    Carl,

    very interesting piece, I discussed it at work with some colleagues. I see you make the classical immunology ‘self/non-self’ distinction. I recently have come to know that a grrl scientist has been rocking immunology foundations by putting this theory in doubts. Her name is Polly Matzinger, and the theory she puts forward deny the the ability of the body to distinguish self and non self (how? does the immune system have a list of all protein allowed to be expressed?). Her alternative is that the Immune system only reacts to ‘Danger markers’. So, extraneus cells/viruses only get wiped out when they cause inflammation, lysis or other anomalous cell behaviour in the body. She has a host of papers published in Nature, I’m told (haven’t checked yet). Did I wet your appetite? Care to draw up a brief post about her? Cheers

    Luca

  11. #11 Paras Chopra
    August 11, 2006

    I don’t see anything freaky here. If we can explain the phenomena (by evolution), why should we be surprised to find it in nature. Finding a scientific proof of super-natural things, for example, can be regarded as freaky.

  12. #12 AgnosticOracle
    August 11, 2006

    Update, 8/10 9:45 am: I unintentionally broke an embargo for this story.

    When I first read this I parsed it as “I unintentionally broke an embryo for this story.” I went back to re-read the article looking for some obscure stem cell joke.

  13. #13 Clastito
    August 11, 2006

    Very cool. How’s that for a radical evolutionary change? From uterine dog cells to eucaryotic venereal disease….wicked!!!

  14. #14 DragonScholar
    August 11, 2006

    Excellent and educational article, great job putting things into language that is clear.

    The implications of this are fascinating – the idea of part of an animal mutating into something else really is mind-boggling. It also makes me wonder how many diseases or conditions out there may be like this, but we just haven’t looked.

  15. #15 Jason
    August 11, 2006

    Man, this should have been a sci-fi movie.

    A man has a strange form of cancer. Hundreds of years later his cell line spreads as tumors in countless others.

    One day, though, one of the tumors grows into a new version of the long dead man, and he’s immortal. AN immortal killing machine. bwahahahaha!

  16. #16 truth machine
    August 11, 2006

    Perhaps, the scientists suggest, our ancestors had to fight against a different sort of tissue donation: cancer parasites.

    This is confused. We can divide cancers into three categories:

    1) those that the immune system destroys
    2) those that the immune system does not destroy, and kill the host
    3) those that the immune system does not destroy, and do not kill the host

    (3) is the category of a “cancer parasite” like this canine tumor. The immune system reduces the number of incidents of category (2) and (3), putting them in category (1) — its effect against category (2) being far more important. Thus, the immune system fights against cancer generally, not cancer parasites per se.

  17. #17 truth machine
    August 11, 2006

    I don’t see anything freaky here. If we can explain the phenomena (by evolution), why should we be surprised to find it in nature.

    “freaky” does not mean “surprising”.

    http://dictionary.reference.com/browse/freaky

    adj 1: strange and somewhat frightening; “the whole experience was really freaky” 2: conspicuously or grossly unconventional or unusual; “restaurants of bizarre design–one like a hat, another like a rabbit”; “famed for his eccentric spelling”; “a freakish combination of styles”; “his off-the-wall antics”; “the outlandish clothes of teenagers”; “outre and affected stage antics” [syn: bizarre, eccentric, freakish, flaky, off-the-wall, outlandish, outre]

  18. #18 truth machine
    August 11, 2006

    Did I wet your appetite?

    FYI: the word is “whet”.

  19. #19 John Wilkins
    August 11, 2006

    The difference between this sort of cancer and, say, HPV-mediated cancers like cervical cancer on the one hand, and the Tasmanian Devil cancer can be usefully characterised by the terms that Paul Ewald discusses in Evolution of Infectious Disease. Those cancers that are difficult to spread will have selection for benign viruence, while those that are easy to spread will be selected for malign virulence. One might therefore look at the mechanisms of infection as a clue to why Tasmanian devil cancer is so virulent. Perhaps it has to do with the cell or tissue type that is infected. HPV infects (from memory) squamous cells. I wonder what cell type this one infects.

  20. #20 DIO
    August 12, 2006

    Reminds me of the “assimilation” tactics used by the Borgs in Star Trek…

  21. #21 Halo Thane
    August 12, 2006

    just wondering, could some of today’s transmissible genetic entities have similar origins; could some viruses be closer related to their current or former hosts, than to other viruses.

  22. #22 Kevin Walsh
    August 12, 2006

    >Perhaps, the scientists suggest, our ancestors had to fight
    >against a different sort of tissue donation: cancer parasites.
    [snip]

    Thus, the immune system fights against cancer generally, not cancer parasites per se.

    Actually, I think you miss the point here. For many organisms, any “non-self” cells generally don’t belong. How would non-self cells arrive? Without the idea of parasitic cancers, the answer to why immune systems evolved the “destroy non-self cells” strategy seems silly: is it to thwart tissue and organ transplants?

  23. It could be sooo easy to break an embargo with these content management systems (CMS), you have to be very careful to make sure the news release posting date is absolutely correct and right.

    Especially tricky can be translating British Summer Time or Greenwich Meantime into the various timezones used by US-based journals in their news releases.

    Be warned, Science will drop you from their list these days if you even inadvertently break an embargo, and that could be painful for anyone relying on that magazine (and possibly everything under the Eurekalert umbrella) for their embargoed news.

    By the way, I haven’t breached yet, but it could happen on my Sciencebase Blog any day. Tread carefully.

  24. #24 Carl Zimmer
    August 14, 2006

    David–The short-circuit was in my brain, not in the computer, I’m afraid. But it is true that you (or I should say I) pay a price for breaking an embargo, even inadvertently. Tread carefully, indeed.

  25. #25 Phobos
    August 14, 2006

    Wild…er, freaky concept. Given the degree to which dogs and humans spend in contact, are there concerns that this parasite could mutate & find a human host? Or is it just too different/too species-specific for any immediate concerns?

  26. #26 woodsong
    August 15, 2006

    I have to wonder about that. I had a very good friend who had a condition that might well have been this particular cancer–he described it as a “dog cyst”, but in him it was treated as a cancer would be (chemo & radiation), and it eventually killed him. He said his condition was common and benign in dogs, and very rare in humans (30+ known cases in the last 50 years). I still miss him.

  27. #27 Black Lizard
    August 16, 2006

    Very interesting.

    It does remind me somewhat of John Carpenter’s 2004 movie based on John W. Campbell’s short story “The Thing”.

    “Perhaps, the scientists suggest, our ancestors had to fight against a different sort of tissue donation: cancer parasites.”

    Parasites, or off-planet life forms?

  28. #28 Rebecca Skloot
    August 16, 2006

    Totally fascinating and freaky post, Carl. Of course, the first thing I thought of when I read about this was HeLa cells, because that’s all I ever think about (book should be out in ’07). But you’re right, this is far stranger, since this dog-thing essentially became a cell line all by itself … an un-contained cell line that actually causes cancer. Now that’s seriously freaky. And yet another bit of validation for all those scientists of the 50s who were ridiculed for thinking viruses caused cancer … they actually injected HeLa cells into people to prove their point, and the result was similar to the dog cancer: small tumors grew, but soon vanished.

  29. #29 Alan Kellogg
    August 16, 2006

    Rebecca,

    Not a cancer really. More an internal parasite. Internal in a way most other internal parasite could never be.

    a Sticker’s Sarcoma’s cells are not derived from the host’s cells. Mostly the same (canine) genome, but the DNA is not that of the host, and the parasite’s genome has been (so to speak) pared down. It’s a simplified canine genome with a few changes.

    For the nonce I’m suggesting “Sticker’s Parasitic Amorphous Blob”. An animal of the amorphous blog phylum capable of infesting the body cavity of a canine, and requiring support from a canine host to survive. Descending from a particular canine’s cells between 2500 and 200 years ago.

    (You know, about a year ago I observed that in a billion years any one human could be father to phyla. Little did I know that an individual canine had already “fathered” a phylum, and that phylum was child to the dog.)

  30. #30 TokyoTom
    August 17, 2006

    Carl, thanks for an extremely interesting post. Reminds me of what Peter Duesberg said in the recent Harper’s piece on AIDS:

    “The basis of speciation is changing the content and the number of chromosomes,” says Duesberg. “Cancer is essentially a failed speciation. It’s not mutation. Cancer is a species. A really bad breast, lung, or prostate cancer has seventy, eighty, or more chromosomes. Those are the real had guys they’re way outside our species. But it’s a rare kind of species that as a parasite is more successful in its host than the normal host cell is.”

    http://www.harpers.org/OutOfControl.html

    More by Duesberg is here: http://mcb.berkeley.edu/labs/duesberg/cell%20motility.pdf#search=%22failed%20speciation%20duesberg%22

  31. #31 Endy
    August 25, 2006

    Hmm, perhaps researchers could take advantage of the cancers tricks to allow at least temporary tissue replacement.

    As I see it it would make the most sense for the immune system to attack harmful dna(viruses and such), obviously foriegn dna, and last and least harmless non-obviously foriegn dna. Presumably the level of attack based on the levels of threat identification ability.

  32. #32 David Harmon
    August 31, 2006

    How would non-self cells arrive? Without the idea of parasitic cancers, the answer to why immune systems evolved the “destroy non-self cells” strategy seems silly: is it to thwart tissue and organ transplants?

    More likely, a matter of fighting off conventional parasites from the higher orders, including some that got “fought off” for good. Consider that surprisingly few insect species can actually invade our bodies successfully, even given the incentives (“free meat for life!” ;-) ). And I don’t know offhand of any mammal, bird or reptile that itself operates as an internal parasite. Part of the reason why is surely those xenoimmunities.

    Fairly early in the biological arms race, we larger animals established a general “no visitors” policy, enforced by blitzkrieg attacks. That may be inconvenient for transplant recipients, but it’s more so for chest-burster wannabes!

  33. #33 Robert G. Schreib Jr.
    December 28, 2006

    Dear Sirs, A fascinating article! My question is, is this Canine Transmissible Veneral Tumor (CTVT) or Sticker’s sarcoma, a possible anti-cancer symbiotic organism? That is, a DEAD host is worthless to it, it apparently wants to co-exist with its host, so would this form of cancer somehow prevent or fight other forms of cancer from infecting or killing off its host? Also, if sharks, early mammals, etc. had to fight off parasitic cancers, then, would eating such cancers parasites off the dead bodies of such species they ate routinely, impart immunity against these types of cancer? A kind of oral vaccination or innoculation against such diseases? That is, if I had a rare type of cancer tumor, would removing it and dipping in honey and eating it, create immunity to that type of cancer in me or the host originally infected with it? Weird science here!

  34. #34 Ana Hess
    January 10, 2007

    The description of this cancer is what my 4 year old chocolate lab has just been diagnosed with….is there any cure, any diet to make them feel confortable until the end? any research for a cure being done? Send any info, I am hart broken about my dog and any help is welcomed. Thank you.

  35. #35 Mod
    August 18, 2007

    Need a Scientific Second Opinion…

    My dog(age approx 16 months, a male Staffordshire / American Pit bull mix breed) which I chose to rescue has developed a exo-genital tumor near or on it’s penis.

    From 3 hours of research it appears to be a CTVT. I can supply a picture and link it from my website for viewing. I will supply the link in advance.

    http://www.modzilla.com/canine-ctvt.php

    At first glance, a week ago, the size of this mass was approximately 20-30 cm.and oval in shape. In fact, I thought it may be a tick. I tried to remove it by

    heating up a piece of cold steel and backing it(the assumed tick) out. I discovered it was a not a tick. The dermis and the dark reddish mass began to react

    to the heated steel as burned tissue. So I decided to cease my offensive action.

    The mass began to grow rapidly… I am not sure if this is due to my actions or the dog’s reactions by licking its wound site. I observed the dog licking

    it’s wound. I have cleaned the area with alcohol daily.

    My approx 16 month old male dog appears to feel no pain or itching now. He is not licking this tumor very much. If so, very rarely. The size of the mass is

    alarming! from 20-30 cm to nearly 100 cm and the volume of blood which has filled the mass is incredible.

    I am fairly poor in money so I am asking for a second opinion here. Please view the image and respond to this blog. If the mass appears to be like a CTVT.

    Please advise the prognosis/sugery procedures that can be expected before going to a Vet.

    I have raised and bred different animals, reptiles, birds and so forth. I have never seen anything quite as aggressive as this type of tumor.

    #######################

    If it appears to be a CTVT what should be done?

    Should I excise this tumor? If excising is recommended then can this be achieved via the following means:

    (1) Lidocaine injection around tumor
    (2) Excision by cold steel
    (3) Using heated metal(under local anesthetic) around surrounding tissue to dissuade regrowth of this virulent tumor.
    (4) What is the best dressing or ointment after excision?

    #######################

    Should I leave it alone?

    Is this a death sentence for my dog?

    What is to be expected in terms of price by Vet to remove this tumor? I need some help here please, as I have the intelligence, skill, and life experience to deal with this myself and an RN who can supply elements necessary for me to do this minor surgery. I feel with 3 hours of research it is daunting to make this decision alone.

    Regards,

    Mod.

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