My post yesterday, criticising the idea that cancer cells provide a window into what single-celled life looked like about a billion years ago, got me reflecting on the incidence of cancer in different organisms. All organisms have to control their cell numbers and coordinate cell proliferation rates, so we should expect cancer to be a feature of all multicelled life. However, the one organism that I am most well acquainted with, apart from myself, doesn’t seem to particularly prone to cancer. This tiny (adults are 1-2 mm long) nematode worm, called Caenorhabditis elegans, or just C. elegans to it’s friends, rarely acquires the kinds of tumours that can be readily observed in other animals. When I mention this as a throw away line in non-specialist seminars, this is often seized upon in the question and answer sessions that the follow the seminar. So, why is this, and should we rush out and start making elixirs from ground up nematode worms as anti-cancer agents? Sadly the answer is no. The reason why cancer is rare in C. elegans is to do with basic differences between how cell numbers are maintained in worms compared to mammals.
At the molecular level there are lots of similarities between worms and us: most of the same molecular pathways that go wrong in human cancer are present in C. elegans (and we can use it as a powerful experimental system to study their properties), and many of the same defects that underlie cancer in humans do cause excessive cell proliferation in C. elegans, it’s just that the effects are rather modest. C. elegans somatic cells seem to be uptight and inhibited compared to their exuberant mammalian counterparts. The extra cells generated are generally well behaved and simply toe the line joining the other cells that form the tissue in which they are generated.
C. elegans can develop tumours, but only in the germ line cells (the ones that produce the egg and sperm cells). The reason for this is that germ cells are stem cells: a population of cells that are maintained throughout the life of the animal, which continue to divide and produce new cells. This creates a continual conveyer belt of cells that gradually turn into sperm or eggs (most C. elegans are females that for a short time can make sperm, which they store to fertilise the eggs that they subsequently make: they have no need for males and thus are the ultimate feminist model organism). In order to become egg or sperm cells though, the cells have to stop dividing. When things go wrong with the mechanism that switches off cell division, as happens in worms carrying certain mutations, the cells never stop dividing, resembling the behaviour of cells in human cancers. In other words the only cells that form genuine tumours in C. elegans are stem cells. This is certainly significant, since our current theory for the origin of human cancers is that they arise either from stem cells, or from cells with stem cell-like properties.
So, the likely reason why C. elegans doesn’t really get cancer is that, unlike in mammals (and many other animals) there are no adult somatic stem cells that can serve as the origin of a tumour. Every adult C. elegans has precisely 959 somatic cells; a strikingly small number of cells compared to our tens of trillions of cells. Importantly, if any of these cells die they cannot be replaced by new cell division since there are no somatic stem cells to provide replacement cells. In contrast, we are profligate with our cells, and can easily afford to replace lost cells by the generation of new cells from our many stem cell populations (such as the mesechymal cells in our bone marrow that generate a variety of cell types, including the red and white blood cells that are constantly lost through cell death). Being able to replace damaged and decrepit cells is clearly a significant boon, but one that comes at a cost. The price we pay for this advantage is cancer.
Kirienko, N. V., Mani, K., & Fay, D. S. (2010). Cancer models in Caenorhabditis elegans. Developmental dynamics 239, 1413–1448. doi:10.1002/dvdy.22247