IL-6 is dispensable for causing cachexia in the colon carcinoma 26 model.
IL-6 is dispensable for causing cachexia in the colon carcinoma 26 model.
复制标题
IL-6对于结肠癌26模型中引起恶病质不是必需的。
DOI：
10.1101/2023.05.02.539076
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hui,Sheng
中科院分区：
文献类型：
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作者：
Kwon,Young-Yon;Hui,Sheng
多种细胞因子与癌症恶病质有关。其中一种细胞因子是 IL-6，它被认为是接种结肠癌 26 (C26) 细胞的小鼠的关键恶病质因子，结肠癌 26 (C26) 细胞是最广泛使用的癌症恶病质模型之一。为了测试 IL-6 在癌症恶病质中的因果作用，我们使用 CRISPR/Cas9 编辑来敲除 C26 细胞中的 IL-6。我们发现 IL-6 KO C26 肿瘤的生长显着延迟。最引人注目的是，虽然 IL-6 KO 肿瘤最终达到与野生型肿瘤相似的大小，但恶病质仍然发生，尽管循环 IL-6 没有升高。我们进一步表明，IL-6 KO 肿瘤中的免疫细胞群有所增加，并且在免疫缺陷小鼠中，有缺陷的 IL-6 KO 肿瘤生长得到了挽救。因此，我们的结果证明IL-6作为C26模型中引起恶病质的必要因素无效，并揭示了其通过免疫抑制调节肿瘤生长的重要作用。
Various cytokines have been implicated in cancer cachexia. One such cytokine is IL-6, which has been deemed a key cachectic factor in mice inoculated with the colon carcinoma 26 (C26) cells, one of the most widely used models of cancer cachexia. Here to test the causal role of IL-6 in cancer cachexia, we used CRISPR/Cas9 editing to knock out IL-6 in C26 cells. We found that growth of IL-6 KO C26 tumors was dramatically delayed. Most strikingly, while IL-6 KO tumors eventually reached the similar size as wild-type tumors, cachexia still took place, despite no elevation in circulating IL-6. We further showed an increase of immune cell populations in IL-6 KO tumors and the defective IL-6 KO tumor growth was rescued in immunodeficient mice. Thus, our results invalidated IL-6 as a necessary factor for causing cachexia in the C26 model and revealed instead its important role in regulating tumor growth via immune suppression.