Cancer pilfers cell powerhouse

A form of contagious cancer found in dogs and wolves may steal its host's mitochondria to replace its own failing organelles, possibly aiding its survival despite damage from high mutation rates.The results, published in the January 21st issue of Science, may provide clues for hindering the spread of other similar cancers, such as a disease that threatens the endangered Tasmanian devil.

Border collie (Canis lupus familiaris)
Credit: Vanessa Schipani

"This paper is an important step in advancing our understanding of the biology of this fascinating area of transmissible cancers," said linkurl:Matthew Breen,;https://www.breenlab.org/ professor of genomics at North Carolina State University, who was not involved in the research. Canine Transmissible Venereal Tumor (CTVT) is an atypical form of cancer that can be passed between dogs during mating. Normally found on the genitalia, the cancer cells are transferred from one individual to another on contact.Though the high mutation rates typical of cancer likely allowed this tumor to evolve skin to skin transmission over time, in some cases it may also cause its mitochondrial DNA (mtDNA) to completely degenerate, said Clare Rebbeck, a former PhD student in linkurl:Austin Burt's;https://www3.imperial.ac.uk/people/a.burt lab at Imperial College London in the UK and first author on the paper. Without mitochondria, the powerhouses of the cell, the tumors cannot produce the energy needed to support basic cellular functions, such as metabolism and DNA replication and transcription, which eventually results in cell death.But the cancer seems to have evolved an ingenious solution -- steal the host mitochondria to do the job after its own mitochondria succumb to the damage. After conducting phylogenetic analyses of mitochondrial and CTVT sequences from a wide geographic range of dogs and wolves, Rebbeck, now a postdoctoral fellow at Cold Spring Harbor Laboratory in New York, and her colleagues found that the nuclear DNA of the tumors was almost identical to one another, but their mtDNA was often more similar to the mtDNA of dogs than to other tumors, suggesting the cancer had adopted its hosts' mitochondria on at least one occasion. "This research really shows us that this cancer is very unusual," said linkurl:Elizabeth Murchison,;https://www.kings.cam.ac.uk/research/fellows/elizabeth-murchison.html a cancer geneticist at the Wellcome Trust Sanger Institute, who was not involved in the research. "It's telling us that their genomes are doing things we don't expect, like horizontal mitochondria transfer."Previous research suggests that CTVT may have evolved from a tissue macrophage, a type of white blood cell that engulfs and kills invading microbes and foreign particles. If the cells retained their engulfing abilities as they evolved into cancer, this mechanism may explain how the tumors are able to pilfer a host animal's mitochondria, Murchison said.

Tasmanian devil (Sarcophilus harrisii)
Credit: Wikimedia commons/KeresH

Though CTVT isn't deadly, a similar form of transmissible cancer found in the endangered Tasmanian devil is known to be fatal. If the same phenomenon is found in the devil's cancer, the finding may help scientists find a cure for the Australian marsupials. If the tumors' access to host mitochondria can be selectively shut down, the cancer could, in theory, dissipate, said Murchison. The devil cancer, however, is only 20 to 30 years old, she added, where as CTVT is believed to have appeared around ten thousand years ago, around the time that dogs were first domesticated. If the cunning trait of mitochondrial intake required thousands of years of mutations to evolve, it may not apply to the relatively young devil cancer, she noted. "[CTVT] is unique because it's oldest known somatic cell line," said Murchison. "It's given us insight in to what a cell can do when it's had a long time to evolve."C.A. Rebbeck et al., "Mitochondrial capture by a transmissible cancer," Science, 331:303, 2011.
**__Related stories:__***linkurl:Tumor cells spread canine cancer;https://www.the-scientist.com/news/display/24286/
[10th August 2006] *linkurl:The Tasmanian devil's cancer;https://www.the-scientist.com/blog/display/23111/
[11th February 2006]