长寿型啮齿类动物的抗肿瘤机制

啮齿类动物是广泛应用于生物医学的重要模式动物,包括先天性胸腺缺陷型的裸鼠、不患癌的裸鼹鼠(Heterocephalus glaber)和盲鼹鼠(Spalax galili)等。哺乳动物的衰老过程与癌症发生率有关,衰老的程度与患癌机率呈正相关。由于啮齿类动物约占哺乳动物的40%,因此研究长寿型啮齿类动物抗肿瘤机制对于抗癌机制的研究具有十分重要的作用。复制性衰老是啮齿类动物中普遍存在的抗肿瘤机制,但在裸鼹鼠和盲鼹鼠体内发现了独特的抗肿瘤机制：盲鼹鼠主要的抗肿瘤机制是由细胞释放IFN-β,激活p53和Rb信号通路,进而导致细胞集中性死亡;裸鼹鼠的抗肿瘤机制是由高分子量透明质酸引起的早期接触性抑制介导。此外,裸鼹鼠和盲鼹鼠的基因组中还含有高表达与调节细胞死亡和抗炎机制相关的基因。本文对裸鼹鼠和盲鼹鼠的独特抗肿瘤机制进行了综述,以期为该领域的相关研究提供参考。

The anti-tumor mechanisms in long-lived rodents

Rodents, including the nude mice with congenital aplasia of the thymus, cancer-resistant naked mole rat (Heterocephalus glaber) and blind mole rat (Spalax galili), are important model organisms that are widely used in biomedical research. The aging process is closely related to cancer incidence in mammals and the aging degree is positively correlated with the risk of cancer. Since rodents account for 40% of mammals, study of the unique antitumor mechanism in long-lived rodents is very important. Replicative senescence is anti-tumor mechanism that prevalently exist in rodents, however, unique anti-tumor mechanisms have been found in naked mole-rats and blind mole-rats. The cancer resistance of Spalax galili is mediated by cell-released IFN-β which activates p53 and Rb signaling pathway and the cells undergoes concerted cell death while that of Heterocephalus glaber is mediated by high molecular weight hyaluronan (HMW-HA) which causes contact inhibition. In addition, highly expressed pro-cell- death and anti-inflammation related genes are found in the genome of both naked mole-rats and blind mole-rats. In this review, we summarize the anti-tumor mechanisms in both Heterocephalus glaber and Spalax galili, which may provide information for related research.