The naked mole rat (Heterocephalus glaber) a bewitching rodent of East Africa has spellbound scientists. This isn't because millennial scientists are nostalgic about Rufus, a charming naked mole rat, who starred in the animated television series Kim Possible as a nifty pet sidekick of Ron Stoppable. However, over and over again, Rufus' concealed superpower abilities helped save the world, and, they might just do it again, because scientists discovered that cultured cells from naked mole rats exhibit high resistance to tumor growth.
In a 2009 study titled “Hypersensitivity to Contact Inhibition Provides a Clue to Cancer Resistance of Naked Mole Rat” published in the Proceedings of the National Academy of Sciences (PNAS), Dr. Vera Gorbunova et. al stated, “The naked mole-rat (Heterocephalus glaber) is one of the most extraordinary mammals. Naked mole-rats (NMR) live in large subterranean colonies in Africa. The colonies have a eusocial structure with one breeding queen, similar to ants and bees. NMR display exceptional longevity, with a maximum lifespan exceeding 28 years. This is the longest lifespan for a rodent species, and is especially striking, considering the small, approximately 35 g, body mass of the naked mole-rat. In comparison, a similarly sized house mouse has maximum lifespan of 4 years.”
Demonstrating remarkable longevity, one might assume that NMR would be prone to accumulating more gene mutations (in the form of various cancers) as they aged, but that is not the case, rather, NMR are unusually resistant to developing cancer. Dr. Vera Gorbunova et. al state, “Cancer is a major age-related disease in humans, and accounts for approximately 23% of human mortality. In mice, cancer mortality is much higher, where it reaches 90% in some strains. Clearly, to achieve long life, species must possess efficient anticancer mechanisms.” So, this anti-cancer phenomenon of NMR may be a dual role of the anti-aging defense mechanisms that they’ve evolved.
In an interview with Proceedings of the National Academy of Sciences (PNAS), Dr. Gorbunova states that her laboratory was comparing different rodents, and they had no trouble culturing rodent cells, but the naked mole rat was different. After failing to culture the NMR cells, her team finally noticed that the cells wouldn’t reach high density on the plate. Usually cells, normal cells, divide and then they form a dense layer on a plate, but with NMR cells, they would halt much earlier when there was still room on the plate. They realized that the phenomena had something to do with contact inhibition, a anti-cancer mechanism which regulates cell replication. In most cases when two cells contact each other, they try to steer away from each other, so, if there is no space for cell division, a phenomenon occurs where cells will stop growth. On the other hand, cancerous cells lack this mechanism and end up growing out of control. NMR cells are of interest in understanding this mechanism because they demonstrate hypersensitive contact inhibition.
Although early contact inhibition protects these amazing animals from cancer, it's not the only mechanism protecting them because Dr. Gorbunova describes, “There is an assay in soft agar which kind of mimics tumerogenesis in vivo, and if we take mouse cells and introduce certain mutations, they will form colonies in soft agar and they would form tumors in mice. NMR cells with the same set of mutations don’t grow at all. When we eliminate early contact inhibition, they will form small colonies, but they don’t grow to that large tumor size, which shows early contact inhibition is important but it’s not the only thing. There is a lot more to study in understanding how NMR stay cancer free.”
Furthermore, in a 2013 study titled, “High Molecular Weight Hyaluronan Mediates The Cancer Resistance of The Naked Mole Rat,” published in Nature, Gorbunova et. al. found that cultured naked mole rat cells produce a unique, high-molecular-mass form of hyaluronan, which they referred to as HMW-HA. When this substance was removed, Gorbunova and her colleagues found that NMR cells became susceptible to tumor growth, suggesting HMW-HA plays an important role in the rodents' resistance to cancer.
Although the research seems endless, thank you Rufus for being a great model organism in helping scientists to understand the preventative mechanisms of cancer and aging.
