1 Novosibirsk State Medical University, Novosibirsk, Russia.
2 Institute of Molecular Biology and Biophysics, Novosibirsk, Russia.
Int J Immunopathol Pharmacol. 2017 Sep;30(3):308-314. doi: 10.1177/0394632017720055. Epub 2017 Jul 26.
In recent years, the concept of formation of a sufficiently autonomous cytokine network in a malignant tumour has emerged. In this regard, the data on the role of this network and its signalling pathways in the process of metastasis are an interesting topic. The aim of this study was to evaluate the in vitro cytokine-producing potential of mammary adenocarcinoma (MAC; and cells of its microenvironment) from patients with or without metastases in regional lymph nodes (LNs). By enzyme-linked immunosorbent assays of culture supernatants, we studied the cytokine production by biopsy samples of MAC: spontaneous and stimulated by polyclonal activators (PAs: phytohaemagglutinin, concanavalin A and lipopolysaccharide). The levels of spontaneous production of interleukin (IL)-10 and granulocyte colony-stimulating factor (G-CSF) and the amounts of IL-2, IL-10, G-CSF and monocyte chemoattractant protein-1 (MCP-1) produced during stimulation by PAs, as well as the index of stimulation by polyclonal activators (ISPA) for IL-2 production, were lower for MAC with LN metastasis than for MAC without LN metastasis. The levels of spontaneous production of IL-2 and interferon (IFN)-γ and the ISPA for granulocyte-macrophage colony-stimulating factor (GM-CSF) production were higher for MAC with LN metastasis. There were only three pairwise correlations between the produced cytokines that were specific to MAC with LN metastasis: IL-2 and IFN-γ, IL-6 and GM-CSF, and IL-8 and GM-CSF. There were 10 pairwise correlations between the produced cytokines that were specific to nonmetastasising MAC: IL-6 and IL-10, IL-6 and MCP-1, IL-8 and IL-10, IL-8 and MCP-1, IL-10 and G-CSF, IL-10 and MCP-1, IFN-γ and MCP-1, MCP-1 and G-CSF, G-CSF and IL-1Ra, and GM-CSF and tumour necrosis factor (TNF)-α. Our data indicate that metastatic tumours show desynchronisation of many pathways of induction and synthesis of cytokines that are characteristic of nonmetastatic tumours.
近年来，恶性肿瘤中形成足够自主细胞因子网络的概念已经出现。在这方面，关于该网络及其信号通路在转移过程中的作用的数据是一个有趣的话题。本研究旨在评估有或无区域淋巴结（LN）转移的乳腺腺癌（MAC）及其微环境细胞的体外细胞因子产生潜力。通过酶联免疫吸附试验检测 MAC 活检样本的细胞因子产生情况：自发产生和多克隆激活剂（PA：植物血球凝集素、伴刀豆球蛋白 A 和脂多糖）刺激产生。LN 转移的 MAC 中，IL-10 和粒细胞集落刺激因子（G-CSF）的自发产生水平以及 PA 刺激产生的 IL-2、IL-10、G-CSF 和单核细胞趋化蛋白-1（MCP-1）的量，以及 IL-2 产生的多克隆激活剂刺激指数（ISPA）均低于无 LN 转移的 MAC。LN 转移的 MAC 中，IL-2 和干扰素（IFN）-γ的自发产生水平以及 GM-CSF 产生的 ISPA 较高。只有三种与 LN 转移的 MAC 相关的细胞因子之间存在特异性两两相关性：IL-2 和 IFN-γ、IL-6 和 GM-CSF 以及 IL-8 和 GM-CSF。与非转移 MAC 相关的细胞因子之间存在 10 种特异性两两相关性：IL-6 和 IL-10、IL-6 和 MCP-1、IL-8 和 IL-10、IL-8 和 MCP-1、IL-10 和 G-CSF、IL-10 和 MCP-1、IFN-γ和 MCP-1、MCP-1 和 G-CSF、G-CSF 和 IL-1Ra 以及 GM-CSF 和肿瘤坏死因子（TNF）-α。我们的数据表明，转移性肿瘤表现出许多与非转移性肿瘤特征性的细胞因子诱导和合成途径的失同步。
