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Canine cancer revealed to be world's oldest cell line

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August 14, 2006

Brussels, 11 Aug 2006

Scientists and vets have traced a cancer that affects dogs around the world back to a single wolf or dog who probably lived in central Asia over 250 years ago. They found that in the case of canine transmissible venereal tumour (CTVT), it is the cancer cells themselves that are transmitted from one dog to another. Their findings are reported in the journal Cell.

CTVT is usually transmitted between dogs during sexual intercourse, but can also spread through licking, biting and sniffing tumour affected areas.. Although CTVT is a serious disease, it is rarely fatal, and the tumours usually regress after three to nine months, leaving the dogs immune to re-infection. It is found in dogs all around the world, and is relatively common in strays.

It has long been believed that CTVT was spread through the transmission of cancer cells from one dog to the other. However, until now there has been no conclusive proof of this, and some researchers have described finding virus-like particles in the cancer cells, suggesting that a virus is ultimately behind the cancer.

To resolve the issue, a team of researchers lead by Professor Robin Weiss at University College London looked at the DNA of tumour cells from infected dogs from five continents and compared this with the dogs' own DNA. They found that in every case, the tumour cells were genetically different from the dogs' cells, showing that the cancer cells came from a different dog.

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Furthermore, comparisons of all the tumours revealed them to be almost identical genetically, indicating that the cancer originated in one dog and then spread across the globe.

The researchers' next task was to try to pin down when and where the cancer arose. To do this they compared the DNA in the tumours to the DNA of various breeds of dog. Their results showed that the source of the disease was probably a wolf or an old Asian breed of dog, such as a husky or shih tzu. Variations in the DNA of the tumour samples suggest that the disease arose relatively recently, between 250 and 1,000 years ago.

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'CTVT has evolved into a cellular parasite that has gained independence from and long outlived its original host,' write the authors of the paper.

The research has a number of important implications for our understanding of cancers and how they are transmitted. CTVT represents the longest living cancer 'clone' known to science. It contradicts the current view that cancer cells generate more and more mutations and inevitably become more aggressive if untreated.

In an accompanying article, Bridgett vonHoldt and Elaine Ostrander of the University of California and national Institutes of Health respectively explain that the cell line's success can be attributed to its mode of transmission. 'Although direct contact is generally not a highly efficient mode of transfer, CTVT takes advantage of the 'popular sire' effect of domestic dogs,' they write. 'A single male can produce dozens of litters over his lifetime, allowing the tumour to affect many more females than it could if a monogamous species were the host.'

As for evidence that the cancer does not seem to have become more aggressive over time, Professor Weiss and his colleagues point out that CTVT would not have been able to infect dogs worldwide if it killed them too quickly. As it is sexually transmitted, it effectively needs to keep female hosts alive until their next oestrus cycle.

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The research could have implications for conservation; the endangered Tasmanian Devil is currently under threat from a cancerous disease which appears to be caused by transmissible cancer cells. The methods used by Professor Weiss and his colleagues could determine if the Tasmanian Devil's cancer is also caused by a 'parasitic' cancer.

Finally, this study has implications for human medicine. 'Our findings show that cancer cells can evade immune responses and CTVT is particularly smart in this regard,' explained Professor Weiss. 'On rare occasions cancer cells have been transmitted from one human to another by hiding in organ transplants. Because the recipient is treated with immunosuppressants in order to prevent rejection, the transferred cancer cells can then grow into tumours just like CTVT. That is why people who have suffered from cancer should not become organ donors.'


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