High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat

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Tian Xiao; Azpurua Jorge; Hine Christopher; Vaidya Amita; Myakishev Rempel Max; Ablaeva Julia; Mao Zhiyong; Nevo Eviatar; Gorbunova Vera; Seluanov Andrei

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Journal: Year:2022 | Volume:6 | Issue:11 Page(s): 187-188

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Title

High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat

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Keywords

Cancer

Hyaluronic acid

Longevity

Naked mole rat

Abstract

The Naked mole rat (Heterocephalus glaber) displays exceptional Longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the Naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their Longevity, Naked mole rats show an unusual resistance to Cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of Cancer. Here we identify a mechanism responsible for the Naked mole rat's Cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signaling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signaling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that Naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide Cancer resistance and Longevity to this species.

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APA: Copy

Tian, Xiao, Azpurua, Jorge, Hine, Christopher, Vaidya, Amita, Myakishev Rempel, Max, Ablaeva, Julia, Mao, Zhiyong, Nevo, Eviatar, Gorbunova, Vera, & Seluanov, Andrei. (2022). High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. IRANIAN JOURNAL OF BIOLOGY, 6(11 ), 187-188. SID. https://sid.ir/paper/1043602/en

Vancouver: Copy

Tian Xiao, Azpurua Jorge, Hine Christopher, Vaidya Amita, Myakishev Rempel Max, Ablaeva Julia, Mao Zhiyong, Nevo Eviatar, Gorbunova Vera, Seluanov Andrei. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. IRANIAN JOURNAL OF BIOLOGY[Internet]. 2022;6(11 ):187-188. Available from: https://sid.ir/paper/1043602/en

IEEE: Copy

Xiao Tian, Jorge Azpurua, Christopher Hine, Amita Vaidya, Max Myakishev Rempel, Julia Ablaeva, Zhiyong Mao, Eviatar Nevo, Vera Gorbunova, and Andrei Seluanov, “High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat,” IRANIAN JOURNAL OF BIOLOGY, vol. 6, no. 11 , pp. 187–188, 2022, [Online]. Available: https://sid.ir/paper/1043602/en

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