Background/Objectives:The significance of cytokine signaling on cancer progression and metastasis has raised interest in cancer research over the last few decades. Here, we analyzed the effects of three cytokines that we previously reported are significantly upregulated rapidly after the surgical removal of primary breast, colorectal, and prostate cancer. We also investigated the regulation of their cognate receptors.Methods:All experiments were conducted using the PANC-1, SW620, and MCF-7 cell lines, treated with three different cytokines (TGF-β1, HGF, and IL-6). The effect of these cytokines on the expression of epithelial–mesenchymal transition (EMT) cell surface markers and neuraminidase-1 activity was measured via fluorescent microscopy and image analysis software.Results:The findings show that these cytokines increase the expression of mesenchymal markers while reducing epithelial markers, corresponding to the EMT process. A strong link between cytokine receptor signaling and the Neu-1-MMP-9-GPCR crosstalk was identified, suggesting that cytokine receptor binding leads to increased Neu-1 activity and subsequent signaling pathway activation. Oseltamivir phosphate (OP) prevented sialic acid hydrolysis by neuraminidase-1 (Neu-1), leading to the downregulation of these signaling cascades.Conclusions:In concert with the previous work revealing the role of Neu-1 in regulating other glycosylated receptors implicated in cancer cell proliferation and EMT, targeting Neu-1 may provide effective treatment against a variety of malignancies. Most significantly, the treatment of patients with specific inhibitors of Neu-1 soon after primary cancer surgery may improve our ability to cure early-stage cancer by inhibiting the EMT process and disrupting the ability of any residual cancer cell population to metastasize.
背景/目的：在过去的几十年中，细胞因子信号传导对癌症进展和转移的重要性引起了癌症研究领域的广泛关注。本研究分析了三种细胞因子的作用，这些因子在我们先前的研究中被发现在原发性乳腺癌、结直肠癌和前列腺癌手术切除后迅速显著上调。同时，我们也探讨了其相应受体的调控机制。 方法：所有实验均使用PANC-1、SW620和MCF-7细胞系，并采用三种不同细胞因子（TGF-β1、HGF和IL-6）进行处理。通过荧光显微镜和图像分析软件，测量了这些细胞因子对上皮-间质转化（EMT）细胞表面标志物表达及神经氨酸酶-1活性的影响。 结果：研究结果显示，这些细胞因子能增加间质标志物的表达，同时减少上皮标志物的表达，这与EMT过程相符。研究发现细胞因子受体信号传导与Neu-1-MMP-9-GPCR串扰之间存在密切联系，表明细胞因子受体结合会导致Neu-1活性增强，进而激活下游信号通路。磷酸奥司他韦（OP）通过抑制神经氨酸酶-1（Neu-1）的水解唾液酸作用，下调了这些信号级联反应。 结论：结合先前揭示Neu-1在调控与癌细胞增殖和EMT相关的其他糖基化受体中作用的研究，靶向Neu-1可能为多种恶性肿瘤提供有效治疗策略。最重要的是，在原发性癌症手术后不久使用Neu-1特异性抑制剂治疗患者，可能通过抑制EMT过程并破坏任何残留癌细胞群的转移能力，从而提高我们治愈早期癌症的能力。
肿瘤(癌症)患者之家