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Of Dogs and Devils. A story of transmissible cancer.
Hero dog Kabang ready to go back to Philippines after surgeries and treatments
Have you heard about Kabang, the hero dog?
She is not the only one of our four-legged friends who helped us out in our times of need, but perhaps the most famous. And here I am not talking about just showering us with their love, but about saving our lives.
Kabang’s story was published in many newspapers and magazines a couple of years ago, and it is also found in Wikipedia http://en.wikipedia.org/wiki/Kabang. In short, when two little girls were crossing a street in the Philippines, a motorcycle approached, and they were in danger of being hit. Kabang, seeing the danger, jumped at the motorcycle, thereby preventing the accident. None of the humans involved were injured, but Kabang suffered serious injuries to her nose, which led to complications such as infections etc. When people read about her story in this country, they organized a campaign to raise funds for reconstructive surgery for the hero dog. The surgery was indeed completed, and Kabang, healed, could return home.
This is a heartwarming story of caring people and a happy ending, which could be the main point of this writing. But it is not. Kabang has also been treated before her surgery for a preexisting condition of transmissible cancer. Transmissible cancer? Does that really exist? Yes, but according to scientists, there are only 2 examples of this disease. One is the canine transmissible venereal tumor which Kabang had, and the other is the devil facial tumor disease. We are talking about the Tasmanian devil, an ‘iconic’ marsupial of Australia, with a voracious appetite.
How do we know that these two diseases are really transmissible? In these two cases the cancer cells in different animals have identical chromosomal makeup, which differ from from the host cells. In other, non-transmissible cancers, the disease arises independently in each animal. (Belov, 2012).
Tasmanian Devil in defensive stance, at Tasmanian Devil Conservation Park.
How can this happen, and if it can, why are there only two examples that we know of? The immune system should recognize and destroy cancer cells derived from another individual. (The immune system also recognizes cancer cells arising from its own tissues. Clearly, this process is not fail-safe, and cancer cells can hide from destruction. However, cells from an other organism should be destroyed efficiently.) Special conditions have to prevail for cancer cells to evade the immune system to be transmissible (luckily), and these likely depend upon both the tumor cells and on the immune makeup of the recipient, as well some other factors. For example, the devil’s deadly disease arose in one individual, and its rapid spread is probably due an unfortunate combination of events, such as the frequent biting of each other’s face during social interactions among Tasmanian devils (http://www.the-scientist.com/?articles.view/articleNo/41292/title/The-Devil-s-Details/).
How do these two transmissible cancers measure up against each other? There is a world of difference between the dog’s and the devil’s disease. Whereas in healthy dogs the tumor regresses within about 6 to 9 months after which the dog gains lifelong immunity, the disease is lethal for devils. The transmissible cancer has caused a decline of 95% in the population of devils in some areas since 1996. The cancer has a 100% mortality, and metastasizes quite frequently. These days, most animals are infected by the time they are 2 years old, and very few live longer than 3 years. The Tasmanian devil is now an endangered species.
So how do the facial tumor cells hide from immune surveillance? Hiding away almost certainly has to do with molecules called the Major Histocompatibility Compex (MHC) that also determine graft rejection. Low diversity among these molecules has been suspected to be responsible for the failure to recognize foreign cells. The latest research, however shows that the most likely reason for the relentless success of the cancer cells is that the Major Histocompatibility Antigens are not made in these cells, so there is nothing for the immune system to recognize (Siddle et al, 2013). The authors suggest that vaccination with cancer cells that had their MHC production up-regulated may be one way to protect the devils from the deadly infection.
Tasmanian Devil at the Tasmanian Devil Conservation Park in Taranna.
The canine cancer is ancient compared to the devil’s disease: it arose about 6000 years ago, whereas the devil's facial tumor was first observed in 1996. The dog cancer has had a longer time to be tamed such that it down-regulates MHC class I expression during tumor transmission, and then up-regulates it to enter a stationary phase. Thus after a while, the disease in dogs stabilizes or regresses. If the devil population is not wiped out, with time the disease in that population may take a similar turn and evolve into a less devastating form.
But hopefully, vaccination or other treatment will save the devils before they – and their disease –will be put to evolution’s merciless test.
Jesse Jenkins (2014) The Devils Details The Scientist http://www.the-scientist.com/?articles.view/articleNo/41292/title/The-Devil-s-Details/
Siddle HV, Kreiss A, Tovar C, et al. ( 2013) Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer. Proc Natl Acad Sci U S A. 110(13):5103-8
Belov K., (2012) Contagious cancer: lessons from the devil and the dog. Bioessays. 2012 Apr;34(4):285-92