Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Pathol Oncol Res. 2022 Aug 30;28:1610555. doi: 10.3389/pore.2022.1610555. eCollection 2022.
The biological macromolecule cell-wall skeleton (Nr-CWS) has well-established immune-stimulating and anti-tumor activities. However, the role of Nr-CWS on natural killer (NK) cells remains unclear. Here, we explore the function and related mechanisms of Nr-CWS on NK cells. Using a tumor-bearing model, we show that Nr-CWS has slightly effect on solid tumor. In addition, using a tumor metastasis model, we show that Nr-CWS suppresses the lung metastasis induced by B16F10 melanoma cells in mice, which indicates that Nr-CWS may up-regulate the function of NK cells. Further investigation demonstrated that Nr-CWS can increase the expression of TRAIL and FasL on spleen NK cells from Nr-CWS treated B16F10 tumor metastasis mice. The spleen index and serum levels of TNF-α, IFN-γ, and IL-2 in B16F10 tumor metastasis mice treated with Nr-CWS were significantly increased. , the studies using purified or sorted NK cells revealed that Nr-CWS increases the expression of CD69, TRAIL, and FasL, decreases the expression of CD27, and enhances NK cell cytotoxicity. The intracellular expression of IFN-γ, TNF-α, perforin (prf), granzyme-B (GrzB), and secreted TNF-α, IFN-γ, IL-6 of the cultured NK cells were significantly increased after treatment with Nr-CWS. Overall, the findings indicate that Nr-CWS could suppress the lung metastasis induced by B16F10 melanoma cells, which may be exerted through its effect on NK cells by promoting NK cell terminal differentiation (CD27CD11b), and up-regulating the production of cytokines and cytotoxic molecules.
生物大分子细胞壁骨架（Nr-CWS）具有良好的免疫刺激和抗肿瘤活性。然而，Nr-CWS 对自然杀伤（NK）细胞的作用尚不清楚。在这里，我们研究了 Nr-CWS 对 NK 细胞的功能和相关机制。使用荷瘤模型，我们表明 Nr-CWS 对实体瘤几乎没有影响。此外，使用肿瘤转移模型，我们表明 Nr-CWS 抑制了 B16F10 黑色素瘤细胞诱导的小鼠肺转移，这表明 Nr-CWS 可能上调 NK 细胞的功能。进一步的研究表明，Nr-CWS 可以增加 Nr-CWS 处理的 B16F10 肿瘤转移小鼠脾 NK 细胞中 TRAIL 和 FasL 的表达。Nr-CWS 处理的 B16F10 肿瘤转移小鼠的脾指数和血清 TNF-α、IFN-γ 和 IL-2 水平显著升高。使用纯化或分选的 NK 细胞的研究表明，Nr-CWS 增加了 CD69、TRAIL 和 FasL 的表达，降低了 CD27 的表达，并增强了 NK 细胞的细胞毒性。Nr-CWS 处理后，培养的 NK 细胞中 IFN-γ、TNF-α、穿孔素（prf）、颗粒酶-B（GrzB）的细胞内表达以及 TNF-α、IFN-γ、IL-6 的分泌均显著增加。总的来说，这些发现表明 Nr-CWS 可以抑制 B16F10 黑色素瘤细胞诱导的肺转移，这可能是通过促进 NK 细胞终末分化（CD27CD11b）和上调细胞因子和细胞毒性分子的产生来发挥作用的。
