Faculty Opinions recommendation of High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.

The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years [1][2][3] .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 4,5 .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 2,6 .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 weight hyaluronan (HA), which is over five times larger than human or mouse HA.This high molecular weight HA accumulates abundantly in naked mole rat tissues due 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 the naked mole rat cells have a higher affinity to HA than the 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 weight HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, Hyal2, naked mole-rat cells become Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.