Contagious canine tumours steal host cell spare parts

Researchers at Imperial College in London have discovered an unusual process which is happening in a contagious form of cancer that infects dogs called canine transmissible...
23 January 2011

Interview with 

Dr Clare Rebbeck, Imperial College


Also in the news this week, researchers at Imperial College London have discovered an unusual process which is happening in a contagious form of cancer that infects dogs. Canine transmissible venereal tumour, or CTVT as it's known, is spread by mating and it can also be transmitted by licking, biting, or sniffing tumour affected areas.  The tumour cells then move from one animal to another and they establish a new tumour.  But what this new study has revealed is that the cancer cells keep themselves healthy by stealing key cellular spare parts from the host animal.  If the same is true of human cancers, it could hold the key to a host of new treatments for the disease and to tell us a bit more, we're joined by Dr. Clare Rebbeck, formerly from Imperial College, she's now at Cold Spring Harbour in the USA, and she's with us.  Hello, Clare.

Clare -   Hi.

Chris -   Welcome to the Naked Scientists.  First of all, can you tell us a bit more about the biology of this tumour, this canine transmissible venereal tumour?

Clare -   So this tumour is actually very interesting.  It's one of only two types of tumour currently known that can be passed on from one individual to another and actually grows like a skin graft.  With the dogs, it's able to go to any type of breed of dogs and can also actually be passed on to some of the wolf population as well.  So, somehow it invades the immune system so the dog is not able to recognize that it's not part of itself and therefore, it doesn't reject the tumour until it grows.

Dogs - Social animals

Chris -   What was the specific question that you were looking to solve with the present study, Clare?

Clare -   So for this present study, we're trying to actually find more information about how the tumours were related to each other and trying to estimate some more information on the age of the tumour.  We have actually done a previous study which tried to calculate how old the common ancestor of all the tumours that we collected were, so we actually collected tumours from seven countries in this particular study.  On the previous study, we found that all the tumours from these countries all came from a single origin and that this was approximately only about 500 or 600 years ago.  We were trying to use the mitochondrial genome for this present study which is another region in the cell which provides genetic information to provide more information about how old the tumour is.

Chris -   So you've got lots of samples of these tumours distributed from various places and you got DNA out of them and specifically DNA from these mitochondria, the little organelles in cells that give cells their energy, but which carry their own DNA so they're useful as a marker.  So how did you then study their mitochondrial DNA?  What were you looking for?

Clare -   So we're looking for mutations in the DNA. Over time, mutations arise and you can actually measure these mutations and they provide information on how closely related one tumour is to another, and also, how long it's been since these tumours have been separated, based on the number of mutations that have arisen between the tumours.

Chris -   And if you compare the numbers of mutations in just the DNA of the tumour, the normal cellular DNA, and the rate at which mutations are cropping up in this mitochondrial DNA, you'd expect them to be the same, were they?

Clare -  Well actually, they're not always the same.  Certain regions in the nuclear genome, which is the area of the genome which most people are familiar with, will mutate much more rapidly.  There's also regions which code for genes and these tend to mutate at a much slower rate.  So we have actually looked at the rapidly mutating regions and found the result from these, about their common ancestor and provide an estimate of their age for this.  The mitochondrial region, or the mitochondrial DNA also has regions which mutates quickly and slowly.  So we actually use both of these regions to help us with the answer that we were looking for, but in both of these regions, the results that we found, we didn't expect them based on their...

Chris -   Why not?  What was wrong?

Clare -   We expected there to be not so many mutations in either region, either the fast or the slowly evolving regions.  But we found actually, there was much more variation between the tumours than we expected..Mitochondria

Chris -   And how do you account for that?  What do you think is going on?

Clare -   Well we think therefore that the mitochondrial genome is actually not part of the tumour per se.  I mean, it hasn't come from a single origin, so we suspected then that the tumour has somehow been able to take up the mitochondrial DNAs from a different source which we suspect would be one of the host dogs, that it had grown on in some point in the past.

Chris -   Do you think it's taking up just the DNA of mitochondria from adjacent host cells or do you think it's scooping up entire mitochondria and bringing them in to the tumour cells to keep them healthy?

Clare -   So that's a good question and we're not entirely sure about that.  We suspect that it's actually taking up the whole mitochondria and so the whole organelle.  We think this because the original type of cell that this tumour came from acts as some sort of immune cell.  So it's able to engulf foreign matter.  So this type of cell, we suspect may then have the ability to engulf the mitochondria itself.

Chris - If this is true, if it is taking up mitochondria on block like this and incorporate them into itself, does this mean the same could happen in any human tumour and this could be one of the reasons why cancers grow so successfully despite being genetically highly disorganized in humans and other animals?

Clare -   I think probably not because the need for it to take up the new mitochondria is mainly a result of the fact that the tumour is so ancient.  In a normal person, their cancer is only as old as the person itself, so the number of mutations may not be sufficient, in order for it to require a new input.  However, this may happen sometimes but it would be very difficult to be able to detect.


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