Kuprash Dmitry V, Qin Zhihai, Ito Daisuke, Grivennikov Sergei I, Abe Koichiro, Drutskaya Ludmila N, Blankenstein Thomas, Nedospasov Sergei A
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Cancer Lett. 2008 Sep 8;268(1):70-5. doi: 10.1016/j.canlet.2008.03.023. Epub 2008 Apr 28.
TNF plays diverse and contrasting roles in cancer, promoting skin carcinogenesis and metastasis, but also possessing potent antitumor effects in mice. TNF via TNFR1 axis induces NFkappaB, and may contribute to inflammation-facilitated neoplasia. On the other hand, lymphomas are cited as rare complications of anti-TNF therapy in humans. In order to address possible modulating role of TNF and of a related cytokine, LTalpha, in spontaneous tumorigenesis, we compared mice with p53-TNF, p53-LTalpha, p53-TNFR1 and p53-TNF-LT combined deficiencies. Unexpectedly, neither of these mice showed significant modulation of their survival or shift in the spectrum of emerging tumors, as compared to p53-deficient mice, arguing against direct link between TNF blockade and lymphoma development.
肿瘤坏死因子（TNF）在癌症中发挥着多样且矛盾的作用，它既能促进皮肤癌发生和转移，但在小鼠中也具有强大的抗肿瘤作用。TNF通过肿瘤坏死因子受体1（TNFR1）轴诱导核因子κB（NFκB），可能促使炎症促进肿瘤形成。另一方面，淋巴瘤被认为是人类抗TNF治疗的罕见并发症。为了探究TNF以及相关细胞因子淋巴毒素α（LTα）在自发肿瘤发生中的可能调节作用，我们比较了p53、TNF、LTα、TNFR1以及TNF-LT联合缺陷的小鼠。出乎意料的是，与p53缺陷小鼠相比，这些小鼠均未表现出存活率的显著变化或新出现肿瘤谱的改变，这表明TNF阻断与淋巴瘤发展之间不存在直接联系。
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