No Comments

Last year one of the books on my reading list was The Immortal Life of Henrietta Lacks, by Rebecca Skloot. I found it a fascinating and moving story. Henrietta Lacks died of cervical cancer, but even before her death doctors had begun to culture cells removed from her cervix (something that was done without her knowledge). Amazingly, these cells didn’t divide a few times and then become senescent; instead, they continued – and continue – to divide without end. HeLa cells are probably one of the most widely used cell lines (they’ve even been up in space) and in that sense, something of Henrietta lives on today.

Recent research indicates that the same is true of the clonal cell line implicated in the Devil Facial Tumour Disease that is killing Tasmanian devils (with population declines of up to 90% in some parts of Tasmania), spread via bites inflicted during social interactions. From the paper just published in PLoS One (Ujvari et al, 2012):

Devil Facial Tumour Disease (DFTD) is a unique clonal cancer that threatens the world’s largest carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii) with extinction. This transmissible cancer is passed between individual devils by cell implantation during social interactions. The tumour arose in a Schwann cell of a single devil over 15 years ago and since then has expanded clonally, without showing signs of replicative senescence; in stark contrast to a somatic cell that displays a finite capacity for replication, known as the “Hayflick limit”.

DFT cells are apparently stable chromosomally, and the tumour cells of different individuals are genetically identical – rather surprising since the tumours have proliferated and their cells passed on to thousands of Tasmanian devils in the short time since DFTD was first identified. This capacity for seemingly endless division is due to the action of the enzyme ‘telomerase’ on structures called telomeres, found on the ends of eukaryote chromosomes.

Normal somatic (body) cells replicate only a few times and then enter ‘replicative senescence’ (Uvjari et al. 2012). This is because the telomeres – tandem DNA repeats bound up with a particular protein complex called ‘shelterin’ – shorten each time the cells divide. The only ‘normal’ cells where this doesn’t happen ** are the cells that give rise to eggs and sperm, due to the action of telomerase, which maintains the length of the telomeres. The same is true for cancer cells.

DFT cells have quite short telomeres, and the research team found that their length is maintained through up-regulation of telomerase gene expression; the shelterin protein complex protects them from continuous elongation. What’s more, it seems that this control is done at the level of individual cells, with up-regulation in cells where telomeres have become shorter over several cycles of cell division, and shelterin blocking further elongation of ‘normal-length’ telomeres. Ujvari & colleagues suggest that

The short telomeres and up-regulation of telomerase likely counteract each other. The short telomeres lead to increased genetic instability but the telomerase activation facilitates tumour growth by either inhibiting further chromosomal instabilities or by circumventing checkpoints that recognise dysfunctional telomeres. Longer telomere lengths may ensure the success and survival of DFT cells by stabilising chromosomal rearrangements and preventing further genomic instabilities.

These features of DFT cells promote survival of the tumours and are the result of natural selection. Coming to a better understanding of the evolution of these features in DFTD could offer useful insights for those seeking to understand tumour development in our own species.

Ujvari B, Pearse A-M, Taylor R, Pyecroft S, Flanagan C, et al. (2012) Telomere Dynamics and Homeostasis in a Transmissible Cancer. PLoS ONE 7(8): e44085. doi:10.1371/journal.pone.0044085

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

In other intriguing research, it appears that mice engineered to have no functioning telomerase age more quickly than normal, but that this decline may be reversed by switching the enzyme back on through adding a particular chemical to their diet. I suppose I should not be surprised to see that the woo-meisters have seized on this: you can purchase a dietary supplement that claims to achieve the same effect in humans (if the glowing testimonials can be believed…)