In a study designed to understand the long lifespan and cancer resistance of the Middle Eastern blind mole rat, researchers have found a completely new cancer defense mechanism.
In a paper published in the Proceedings of the National Academies of Sciences (1), researchers at the University of Rochester describe a phenomenon called concerted cell death. In this mechanism, the rodent’s cells recognize and kill abnormal cells and neighboring cells before they become cancerous. This intervention helps the blind mole rat resist cancer and live up to 21 years.
To simulate cancer, Gorbunova’s lab rapidly grew primary fibroblast cells that were isolated from the rodent in culture. Her team expected to find an anticancer mechanism similar to the one that they recently described in the African naked mole rat called early contact inhibition. That mechanism prevents overcrowding in cell populations by arresting the cancerous cells with uncontrolled growth and proliferation while allowing others to survive.
Instead, Gorbunova and colleagues found that their entire culture died. “We had never seen the entire culture dish die at once before. Within three days, there were no more live cells on the plate,” said Gorbunova.
To investigate the possible biological processes behind their observation, the researchers measured the levels of the protein interferon, which is released by an organism’s cells to initiate an immune system response to pathogens. The team found that interferon was secreted in the cells in the culture in response to the cancer stimulation. As a result, all the cells in the culture died.
The blind mole rat may have evolved this unique use of interferon to protect itself against oxygen deprivation and flooding in its natural underground tunnel habitat. So, the blind mole rats and naked mole rats seem to have evolved two different anti-cancer mechanisms to meet the survival needs of their underground environments.
“Surprisingly, when the same scenario was repeated on different continents, evolution came to two different decisions. It just happened independently, two different solutions to the same problem,” said Gorbunova.
Now, Gorbunova plans to conduct more tests to understand how the blind mole rat’s cells actually sense hyperproliferation and how to use interferon to activate similar pathways in human cells for cancer prevention.
“I do believe that this is very applicable, and I would like to see more cancer researchers actually using those cancer resistance models because it’s a staple organism to use mice that are cancer prone," said Gorbunova. "But if we want to understand cancer resistance, mice are not very useful. It is better to look at species that are cancer resistant.”
1. Gorbunova, V., C. Hine, X. Tian, J. Ablaeva, A.V. Gudkov, E. Nevo, and A. Seluanov. 2012. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. PNAS Early Edition. Published online October 3, 2012.