UR biologists have found that small-bodied rodents with long life spans have evolved a previously unknown anti-cancer mechanism. This mechanism appears to be different from any anti-cancer mechanisms employed by human beings or other large mammals.
Understanding this mechanism may help prevent cancer in humans because many human cancers originate from stem cells and similar mechanisms may regulate stem cell division.
‘We haven’t come across this anti-cancer mechanism before because it doesn’t exist in the two species most often used for cancer research: mice and humans,” a principal investigator of the study and Assistant Professor of Biology Vera Gorbunova said. ‘Mice are short-lived and humans are large-bodied. But this mechanism appears to exist only in small, long-lived animals.”
Gorbunova believes that cells of long-lived, small-bodied rodents are hypersensitive to cues from the surrounding tissue. If these cells sense that conditions are not conducive to growth, they slow down cell division. Such a mechanism would arrest tumor growth and prevent metastases.
Gorbunova discovered that telomerase, an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer, is highly active in small rodents, but not in large ones.
It has been previously assumed that an animal that has a lifespan as long as a human’s needs to suppress telomerase activity to guard itself against cancer.
Telomerase helps cells reproduce. Since cancer is essentially uncontrolled cellular reproduction, an animal living for 70 years has a large amount of time for its cells to mutate into cancer.
A mouse’s life expectancy is shortened by other factors in nature, such as predation, so it was thought the mouse could afford the slim cancer risk to benefit from telomerase’s ability to speed healing.
Gorbunova and colleagues’ research has challenged this previous assumption. Her research showed that it was not life expectancy, but body mass, that regulated the excretion of telomerase.
Simply having more cells increases the likelihood that one will become cancerous. Since humans are large animals, they would likely develop cancer much more often and much earlier if we didn’t suppress our telomerase.
Gorbunova’s research has prompted another question.
Researchers are asking about small animals like the common gray squirrel that live for 24 years or more. With telomerase fully active over such a long period, why isn’t cancer rampant in these creatures?
Gorbunova found that the squirrel, naked mole-rat, chipmunk, muskrat and chinchilla excrete high levels of telomerase. These high levels would be expected to increase their cancer risk over their long lifetimes.
However, these species have developed a mechanism to counteract the high telomerase activity and remain cancer free for the duration of their lifespans.
‘Squirrels know a cure for cancer,” Gorbunova said. ‘Short-lived small species display continuous rapid proliferation of their cells, but these long-lived rodents have somehow found a way to slow down that proliferation when they need to.”
Gorbunova thinks that squirrels and similar rodents have evolved a strict monitoring function within their cells that may be able to sense appropriate and inappropriate cell division, such as healthy reproduction and runaway cancerous reproduction, and slow or inhibit the division if necessary. Gorbunova is now looking to isolate and understand this mechanism with the hope that it may be applicable to help human cells thwart the onset of tumor growth.
Along with Gorbunova and the first author, Andrei Seluanov, the paper explaining this new research was co-authored by Gorbunova’s long-time collaborator Daven
Presgraves. It was also co-authored by members of the Gorbunova laboratory at UR. These include Chris Hine, Michael Bozzella, Amelia Hall and Tais Sasahara, as well as the University of San Paulo’s Antonio Ribeiro and Vanderbilt University’s Ken Catania.
Schneier is a member of the class of 2011.