During my time as an employee at a vet hospital, I have seen rat after rat undergo surgery to remove massive tumors covering the body. It made me curious as to what made rats so susceptible to these tumors. My curiosity diverged me, however, to the naked mole-rat (Heterocephalus glaber) which has been identified as a cancer resistant mammal. Naked mole-rats have a very long life span compared to other rodents, some being known to live past 3o years. Since cancer is the disease of aging, it is significant that this species during its lifespan evades cancer. This species is now being further studied to determine the mechanism by which this occurs and if by understanding the process in naked mole-rats, we can potentially mimic the process the humans.A study by the University of Texas Health Science Center examined naked mole-rat fibroblasts and the ability of naked mole-rat fibroblast cells to not be susceptible to tumorgenicity and metastasis. In this study, naked mole-rat (NMR) fibroblasts were transformed with retroviruses containing oncogenes SV40 and Ras. As we learned in class, Ras mutations become oncoproteins that promote cell growth. At first, these cells expressed growth and begun rapidly dividing, but after 40 population doubling, the cells entered a "crisis" state and growth was arrested. Crisis states usually arise after massive DNA damage or telomere dysfunction and stop the mitotic process. In rats and mice, these retroviruses resulted in full malignant transformations. When samples of NMR transformed cells were implanted into immunodeficient mice, the growths formed were 0.09 cm at largest compared to full invasive tumors in transformed mice cells.
In addition, when samples of cells were taken from NMR transformed cells that had not yet reached a crisis state and implanted in mice, the cells immediately entered a crisis state. This suggests that when NMR cells lose anchorage to other cells, they enter crisis. Without the ability to lose anchorage and still survive, the abnormal transformed cells cannot metastasize. Metastasis is one of the hallmarks of cancer.
The study only concluded that metastasis and tumor growth are inhibited in naked mole-rats. There was little suggested on the mechanism by which NMR cells enter crisis. However it is known from a previous study conducted by the University of Rochester in 2009 that naked mole-rats have a high level of activity in the p16 tumor suppressor gene. The presence of oncogenes reduces the level of activity of tumor suppressor genes. In naked mole-rats, it is possible that the higher initial level before oncogene presence allows a normal level of activity to still be present in cells. Therefore, the tumor suppressor pathway can still work to trigger apoptosis or induce the crisis state.
It is hopeful to know that through understanding this mechanism better through further studies of the NMR, we may be able to find a new cancer preventatives that inhibit metastasis and massive cell growth.
Image used from stinkyrat.com
