Feature: Transmissible cancers
18 March 2010. By Chrissie Giles
Check in any medical dictionary, encyclopedia or website and you'll find cancer listed as a non-communicable disease. Yet transmissible cancers - which can spread between individuals - have been know about for over 130 years, when a Russian vet found that he could successfully transplant a tumour from one dog to another unrelated to it.
Thankfully, no transmissible cancers have been found in humans, although they are known in several animals. We've trawled through the literature and spoken to researchers working in the field to find out the facts about this fascinating but little-known form of cancer.
How does cancer usually arise?
Cancer occurs because of genetic mutations that arise in our cells. These mutations can be inherited from our parents, or caused by carcinogens in the environment, such as cigarette smoke or ionising radiation. Some cancers develop because of infection with a bacterium or virus. For example, chronic infection with hepatitis B and/or C is a major cause of liver cancers across the world.
So, isn't cancer a non-communicable disease?
For the vast majority of cases, the answer is yes. Several so-called transmissible cancers have been identified in nature, although none affects humans.
How do transmissible cancers spread?
Transmissible cancers spread by the exchange of cancer cells from one individual to another. They're also known as parasitic cancers because transmissible cancers have long grown independent from and outlived their original host animal, like parasites.
The cancer cells are transmitted as an allograft - essentially, a tissue transplant between two animals from the same species with different genetic make-ups. Organ donations and tissue grafts are examples of allografts.
Are they different in any other ways?
There's still a lot to understand about transmissible cancers, but one difference between these and non-transmissible cancers is the genetic relationship between the host and the cancer. In most cancers (i.e. non-transmissible ones), the host cell undergoes a series of genetic mutations that 'transform' it into a cancerous cell. This means that the cancer cell genome has similarities to the host cell genome.
In the case of transmissible cancers, the cancer cell originates from the first ever organism to have developed the cancer. For canine transmissible venereal tumour (CTVT), this is thought to be an East-Asian dog or wolf which lived thousands of years ago. This means that the cancer cell is not related genetically to the host cell. It also means that cancer cells taken from different animals with the tumour will be very closely related. Researchers claim that the dog tumour is effectively the oldest continually propagated mammalian cell line in the world.
Why don't these cancers get rejected by the immune system?
Ordinarily, allografts are recognised as foreign by the host's immune system and are attacked. Patients undergoing organ transplants are given immunosuppressant drugs to try and prevent rejection of the organ.
Researchers think that transmissible cancers have somehow evolved to evade host immune responses. In the transmissible cancer of dogs (CTVT), the cancer has been seen to reduce the expression of dog leukocyte antigen (DLA) genes, the molecular system by which the dog's immune system tells the difference between 'self' and 'non-self'. This is thought to help the cancer 'sneak under' the radar of the animal's immune system, allowing it to grow and live within the animal's body - at least for a limited time.
Which organisms are affected?
In addition to the dog, transmissible cancers have been observed in the hamster and Tasmanian devil. No transmissible cancers affect humans, although there are some rare instances in which cancers have been transmitted by the exchange of cancer cells from one person to another (see below).
1. Hamster
How is the hamster affected?
In a paper published in 1961, Darlene Brindley and William Banfield described the spontaneous appearance of a tumour in the top lip of a male laboratory hamster.
What research has been done?
The researchers explored how the tumour spread between the hamsters. Firstly, the tumour spread to healthy hamsters when they were caged with affected hamsters but separated by a screen - the researchers think the physical contact afforded by the mesh was enough to transmit the tumour. The tumour was also spread when healthy hamsters were fed tumour material, and later lab work showed that the tumour could be transmitted by mosquitoes between cancer-bearing and healthy hamsters.
What's the conclusion?
From these findings, the researchers concluded that the physical transfer of cells between hamsters was important. Other research showed that tumours from affected hamsters all had the same chromosomal changes.
References
- Banfield WG et al. Mosquito transmission of a reticulum cell sarcoma of hamster. Science 1965;148(3674):1239-40.
- Brindley DC, Banfield WG. A contagious tumor of the hamster. J Natl Cancer Inst 1961;26;949-57.
2. Dog
How is the dog affected?
Canine transmissible venereal tumour (CTVT) - a transmissible cancer in dogs - was first characterised in 1876. Also known as Sticker's sarcoma, the tumour is spread through sex and by licking, sniffing and biting affected areas.
What research has been done?
Historically, the scientific community has gone back and forth on the question of whether this tumour is spread by viable cancer cells. This was pretty much settled by a paper published in 2006. Murgia et al. showed that tumour samples taken from dogs from five continents were all genetically distinct from their hosts but shared a common origin - proving that the tumour is indeed spread by an allograft. Where normal dogs have 78 chromosomes, CTVT cells from different animals typically have 58 to 59 chromosomes. The original case was thought to have occurred thousands of years ago in a wolf or an East-Asian breed of dog. They also found that the tumour reduces the expression of genes involved in the immune system.
What's the conclusion?
The dog tumour has been around for a long time, and so has developed some mechanisms to avoid rejection by its host. As it's mainly sexually transmitted, its spread requires the animals to live long enough to have sex. This means that it's not a very aggressive disease, and coexists with dogs relatively peacefully. In fact, many dogs eventually mount an immune response and reject the cancer without treatment.
References
- Murgia C et al. Clonal origin and evolution of a transmissible cancer. Cell 2006;126(3):477-87.
- Rebbeck CA et al. Origins and evolution of a transmissible cancer. Evolution 2009;63(9):2340-9.
3. Tasmanian devil
How is the Tasmanian devil affected?
Devil facial tumour disease was first observed on a Tasmanian devil in 1996 by a wildlife photographer in Mount William National Park, north-east Tasmania. Initially dismissed as a single random case of a strange facial growth, the disease began to spread across the island. It is transmitted by the transfer of cancer cells that occurs when devils bite each other on the face, for example, during feeding, fighting and mating. The cancer kills devils within six to nine months and there is no treatment.
What research has been done?
Research published by Australian researchers in 2006 showed that the chromosomes from tumours from 11 different devils were rearranged in a similar way, as they would be if the cancer were spread as an allograft. The spread of the cancer across the island of Tasmania also suggested that it could be transmissible. Recent research has showed that the origin of the tumour is a type of cell found in the nervous system called a Schwann cell.
What's the conclusion?
Modelling studies suggest that the cancer is spread in a frequency-dependent manner, rather than a density-dependent one. This means that the spread depends more on the frequency of interactions between the devils, rather than the number of devils. In theory, the disease could wipe out devils altogether.
For more on this cancer, see the feature on Dr Murchison's research into devil facial tumour disease">devil facial tumour disease, and the Save the Tasmanian Devil Program.
References
- Pearse AM and Swift K. Allograft theory: transmission of devil facial-tumour disease. Nature 2006;439(7076):549.
- Murchison E et al. The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer. Science. 2010;327(5961):84-7.
4. Human
How is the human affected?
No transmissible cancer is known in humans, although there are several documented ways in which cancer cells have been transmitted between people.
What research has been done?
In the US, around 3500 women each year get cancer while they're pregnant. Melanoma, acute leukaemia and carcinoma are examples of cancers that have been passed from mother to fetus. Acute leukaemia cells have also been passed from baby to baby in multiple births. Another possible - but rare - route of tumour cell transmission is organ transplantation. There is also a case of a surgeon who injured his hand during an operation to remove a tumour from the abdomen of a patient. Some five months later, the surgeon found a swelling at the site of injury that was shown to be a tumour with the same genetic origin as that of the patient.
What's the conclusion?
One theory is that cancer is not an infectious disease in humans because we all (identical twins excepted) have different human leukocyte antigen (HLA) genes, allowing our immune systems to differentiate between self and non-self. Some researchers have suggested that the diversity of the HLA system in humans may mainly be to prevent cancer from being transmissible.
References
- Dingli D and Nowak MA. Cancer biology: infectious tumour cells. Nature 2006;443(7107):35-36.
- Welsh JS. Cancer is not always a non-communicable disease. [letter] CA Cancer J Clin 2009;59:282-284.
Top image: Tasmanian devil. Credit: Ian D Williams, Anaspides Photography.
A modified version of this article appears in Wellcome News 62 (March 2010).
