Cancers induce the production of acute phase proteins such as serum amyloid alpha (SAA) in the liver and cause systemic inflammation. Despite the well-known coincidence of acute phase response and systemic inflammation, the direct roles of SAA proteins in systemic inflammation in the cancer context remains incompletely characterized, particularly in vivo. Here, we investigate the in vivo significance of SAA proteins in systemic inflammation in the 4T1 murine breast cancer model. 4T1 cancers elevate the expression of SAA1 and SAA2, the two major murine acute phase proteins in the liver. The elevation of Saa1-2 correlates with the up-regulation of immune cell-related genes including neutrophil markers. To examine this correlation in detail, we generate mice that lack Saa1-2 and investigate immune-cell phenotypes. RNA-seq experiments reveal that deletion of Saa1-2 does not strongly affect 4T1-induced activation of immune cell-related genes in the liver and bone marrow. Flow cytometry experiments demonstrate the dispensable roles of SAA1-2 in cancer-dependent neutrophil infiltration to the liver. This study clarifies the negligible contribution of SAA1-2 proteins in systemic inflammation in the 4T1 breast cancer model.

中文翻译：

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在 4T1 鼠乳腺癌模型中，全身性炎症不需要血清淀粉样蛋白 alpha 1-2

癌症会在肝脏中诱导产生急性期蛋白，例如血清淀粉样蛋白 α (SAA)，并引起全身炎症。尽管众所周知的急性期反应和全身炎症同时发生，但 SAA 蛋白在癌症背景下的全身炎症中的直接作用仍未完全表征，尤其是在体内。在这里，我们研究了 SAA 蛋白在 4T1 小鼠乳腺癌模型中的全身炎症的体内意义。4T1 癌症提高了肝脏中两种主要的小鼠急性期蛋白 SAA1 和 SAA2 的表达。Saa1-2 的升高与免疫细胞相关基因（包括中性粒细胞标志物）的上调相关。为了详细检查这种相关性，我们生成了缺乏 Saa1-2 的小鼠并研究了免疫细胞表型。RNA-seq 实验表明，Saa1-2 的缺失不会强烈影响 4T1 诱导的肝脏和骨髓中免疫细胞相关基因的激活。流式细胞术实验证明了 SAA1-2 在癌症依赖性中性粒细胞浸润到肝脏中的可有可无的作用。本研究阐明了 SAA1-2 蛋白在 4T1 乳腺癌模型中对全身炎症的贡献微不足道。