You poor devil
RadioLab recently updated and rebroadcast their Tumors episode (RL link). This includes a story about President Grant’s tumor kept in a cigarbox in museum archives and one about the transmissible facial tumor plaguing Tasmanian Devils. The tumor, known as Devil Facial Tumor Disease (DFTD) is a rare case of an infectious cancer. This is the one that I wanted to think about some more.
What do we know about tumors? How do they arise? Why is cancer so much more prevalent today than ever before? What makes these Tasmanian Devil tumors especially nasty?
What do we know about tumors?
Actually, quite a lot. And many new therapies are very successful – especially those that target very specific kinds of tumors. In 1963 Todero and Green (http://jcb.rupress.org/content/17/2/299.full.pdf+html) established both a cell line and a precise methodology for growing cells in culture that permitted researchers the ability to recognize specific changes in cells grown in culture – changes such as becoming non-responsive to the presence of other cells that should control cell division.
30 years of p53 research
Over the years a number of tumor suppressor proteins and proto-oncogenes have been identified. These are the proteins responsible for restraining cell cycle in the event of DNA damage. Among these is p53, the most frequently altered protein in cancer. It was originally identified in 1979 and has since been shown to arrest cell cycling in the event of DNA damage, initiate repair protocols and start a ‘countdown’ to self-destruction (apoptosis).
A number of additional mutations have been defined in proteins that either promote cell cycle progression (proto-oncogenes) or arresting cell cycle progression. Each of these proteins may be mutated in a different way, but the outcome is always the same: cells are pushed through their cycle despite the presence of DNA damage.
Beyond this, more processes have been found to contribute to tumor success. Some tumors promote angiogenesis (the growth of new blood vessels) to feed the tumor. Some have mutations that allow them to break off of the main tumor mass and survive in the blood or lymph and migrate to new areas. Some tumors perform tricks to escape recognition by the immune system.
In time, successful tumors may do all of these things. And how can they mutate so quickly and skillfully? It all goes back to p53. When a cell doesn’t slow down and correct errors in its DNA – and when it does not self-destruct when these errors are too damaging, the cell is free to mutate again and again. Each mutation is like a new child that either does better or worse in its environment, with only the successful ones living to spread their genes.
How do they arise?
Tumors arise when DNA damage occurs in just such a way that it escapes notice by the cell and starts to multiply. Actually, we think that a lot of tumors start up, but get weeded out by our immune system again and again. The ones we see are those that were successful enough to evade our defences and grow up. (immune surveillance: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857231/)
Why is cancer so much more prevalent today than ever before?
Because we live so much longer. The increase in cancer rates does not come from cancer becoming worse over the years, but comes from the fact that we live long enough to get it
We’re getting old … Unfortunately, that means we’re getting cancer too
What makes these Tasmanian Devil tumors especially nasty?
Transmissible tumors are rare because of the conditions required to allow for them are also very rare. In the case of DFTD the stars aligned in just the right way to allow this to occur.
The first requirement is that a tumor must have evolved sufficiently to be able to spread throughout the body of the initial host and be expressed on the face of this animal.
Second, this tumor was amazing in that it could start growing even in new animals if cells should be transferred from one to another. This may have something to do with the uniformity of the devil population and/or the way that these tumors ‘hide’ cellular markers that would otherwise expose them as bad/ foreign cells. The latter of these explanations is supported by data such as: pnas “reversible epicene tic down-regulation of MHC by devil facial tumor…” Siddle et al vol. 110 no. 13
(my question now is: don’t these devils have NK cells that should eliminate these MHCI-deficient cells?)
Perhaps most importantly, these tumors affect animals that are naturally aggressive towards other members of their species in both feeding and sex. Because devils bite one another so often, they provide just the right opportunity for cells to jump from one animal to another.
There is a similar case of a canine transmissible tumor (“tumor cells spread canine cancer” in the scientist, August 10, 2006 by Melissa lee Phillips.) but other than that, these types of tumors are not often seen.
Altogether, this is a fascinating case that illustrates some peculiarities of tumors, DNA damage control and immunology.
The devastating effect of this tumor epidemic is that it has precipitated a dramatic decline in devil numbers now making them endangered of extinction.
Visit the ‘Save the Tasmanian Devil’ website for more information about their condition. (: http://www.tassiedevil.com.au/tasdevil.nsf)
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