裸鼹鼠引人瞩目之处在于它们寿命极长,同时对癌症几乎有完全的抵抗力。现在,一个新颖的糖胺多糖变体被发现是它们抗癌能力的一个关键贡献因素。该变体使这种动物具有在地下生活所需的结实而柔和的皮肤。透明质酸是细胞外基质的一个普遍成分。Xiao Tian等人发现,裸鼹鼠成纤维细胞的培养介质会因一种粘稠物质的积累而变得有粘性,同时他们还识别出该物质是一种“高分子量透明质酸” (HMM-HA) ,比小鼠和人类的相应物质大5倍。它因透明质酸酶活性低以及一种独特形式的“透明质酸合成酶-2”的存在而在裸鼹鼠组织中积累。HMM-HA 通过 CD44 受体发挥作用,HMM-HA的清除使得裸鼹鼠细胞更易发生变形。这种不同寻常的抗癌形式为研究抗癌及寿命延长策略提供了潜在的新途径。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi: 10.1038/nature12234
High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat
Xiao Tian, Jorge Azpurua, Christopher Hine, Amita Vaidya, Max Myakishev-Rempel, Julia Ablaeva, Zhiyong Mao,Eviatar Nevo, Vera Gorbunova & Andrei Seluanov
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 nakedmole-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 signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once highmolecular-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.