Wednesday, June 25, 2014

Cancer Pre-Dates Vertebrates: new evidence shows the disease is as old as mutli-cellular life

Members of the genus Hydra
Will we ever live to see the day when cancer is eradicated?  Apparently not, according to German scientist Thomas Bosch.  As it turns out, cancer pre-dates vertebrates, it is as old as multi-cellular life.  We have a fairly good understanding of the nature of tumor development in vertebrates, but until now, we had no knowledge of the incidence and development of tumors in invertebrates, and definitely not outside of the bilateral clade.  A new study, published in Nature Communications, is the first ever to find evidence of naturally occurring tumors in two species of Hydra.  These results indicate that the molecular basis for cancer development came about very early in evolutionary history.

Members of the genus Hydra are small, simple fresh-water animals.  They are predatory, eating primarily small invertebrates like Daphnia and Cyclops.  They are typically sedentary, but they can move around, especially when hunting, using a somersaulting motion (there are lots of videos of this on youtube).

They have a very simple body plan, composed of only two cell layers.  They don't have muscles or brains, only a basic epidermis on the outside and a gastrodermis on the inside, which are separated by a gelatinous substance called mesoglia.  Hydra usually reproduce asexually by budding (and live practically as immortal organisms) when environmental conditions are good, and sexually when conditions are harsher.  In these organisms, the differentiation between body cells and gametes (sex cells) is mediated by interstitial stem cells (ISCs).

Hydra species with tumors
When the researchers examined the cells of the Hydra, they found that the abnormal tissue bulges contained large amounts of cells that looked like ISCs.  They were clustered, had large nuclei, and effectively did not look like normal body cells.  Size-wise, these tumor cells resembled gametes.  But unlike the development of gametes, the tumor cells never matured into egg cells. 

Tumors in Hydra are the
result of arrested gamete
To look at this phenomenon at the molecular level, Dr. Bosch and his team looked at where specific marker proteins went in the cells.  What they found is that the tumor cells were specific to female lines, they were a result of arrested cell differentiation rather than unimpeded cell proliferation, and they were resistant to the normal apoptotic control mechanisms that usually allow for the formation of egg cells.  

When the authors looked at overall gene expression in both the normal and the tumor-affected Hydra, they found that the tumors have a very distinct gene expression profile that was quite different from the normal female Hydra cells - and that this difference in gene expression occurs very early on in egg development.  In other words, while the process of egg and tumor development start out the same in Hydra, the differences in gene expression between the two cell types is what leads to a normal sexually reproducing Hydra, and a tumor-affected Hydra.

Unfortunately, the exact origin of Hydra tumor cells remains unknown, but we do know that cancer is older than vertebrates, and older even than bilateral organisms.  Clearly, even organisms like Hydra, which are technically capable of immortality, are not exempt from getting cancer.  It's not all bad news though: the authors are optimistic that being able to trace back the evolution of cancer to its roots will help us fight it.  Clearly, species of Hydra have an enormous amount of information to help us understand this complex problem.

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