Anti-Wrinkle Compound Found in Naked Mole Rat Goo May Prevent Cancer
The naked mole rat is an exceptional species of rodent for two reasons: One, it lives nearly 8 times longer than the common house mouse. Two, naked mole rats don’t get cancer—ever.
While the reason for its long life span has eluded scientists, its apparent immunity to cancer may have finally been discovered as reported in a recent article published in the journal Nature. According to the authors of the study, naked mole rat skin cells called fibroblasts secrete an extremely high-molecular-mass hyaluronan (HA) that apparently protects naked mole rats from cancer.
Hyaluronan is a glycosaminoglycan molecule that is ubiquitous in connective, epithelial, and neural tissues and is one of the chief components of the extracellular matrix that gives skin its elasticity. Hyaluronan is sometimes injected into skin to remove wrinkles. And, it is also injected into the knee joints for the treatment of pain in individuals with osteoarthritis due to that hyaluronan is very similar to the synovial fluid found in joints and acts as a lubricant and shock absorber.
According to a news release issued by the University of Rochester, the discovery of the extremely high-molecular-mass hyaluronan was precipitated by noticing that naked mole rat cell cultures produced a gooey substance that was clogging up the vacuum pumps and tubing used in cell cultures. This gooey mess was not observed in cell cultures of other animal types.
Analysis of the goo revealed that it is a form of hyaluronan coded by a HAS2 gene found in mice and humans, but differs slightly in naked mole rats resulting in synthesis of HA molecules that are over five times larger than human or mouse hyaluronan. The hyaluronan is also present in naked mole rat bodies at much higher concentrations than the human and mouse form is in their bodies.
The researchers discovered that when the HA goo was removed from the cell culture that the cells then became susceptible to tumor formation. Furthermore, they found that when the extremely high-molecular-mass HA is removed from cells by knocking out the HAS2 gene, or by causing an overexpression of a HA-degrading enzyme called “HYAL2,” the naked mole-rat cells become susceptible to forming into malignant tumors when transplanted into mice.
The researchers posit that the high molecular weight hyaluronan is responsible for activating an anti-cancer gene called p16 that stops the proliferation of cells when too many of them crowd together. They also posit that this form of naked mole rat hyaluronan could work similarly in humans.
"A lot of cancer research focuses on animals that are prone to cancer," says study co-author Gorbunova. "We think it's possible to learn strategies for preventing tumors by studying animals that are cancer-proof."
The University of Rochester news release notes that future studies from the research team will focus on determining whether the HMW-HA from naked mole rats may have clinical value for either treating or preventing cancer in humans.
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Reference: “High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat” Nature, Published online 19 June 2013; Xiao Tian, Jorge Azpurua, Christopher Hine, Amita Vaidya, Max Myakishev-Rempel, JuliaAblaeva, Zhiyong Mao, Eviatar Nevo, Vera Gorbunova, and Andrei Seluanov.