Autenshlyus A I, Davletova K I, Studenikina A A, Mikhaylova E S, Varaksin N A, Zhurakovsky I P, Proskura A V, Sidorov S V, Lyakhovich V V
Novosibirsk State Medical University, Novosibirsk, Russia; Institute of Molecular Biology and Biophysics, Novosibirsk, Russia.
Novosibirsk State Medical University, Novosibirsk, Russia.
Biomed Khim. 2019 Aug;65(5):424-431. doi: 10.18097/PBMC20196505424.
The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.
本研究旨在研究血液免疫细胞、肿瘤及其微环境中细胞因子的产生,并对非特殊类型浸润性导管癌伴淋巴转移患者的细胞外基质进行表征。在95例非特殊类型浸润性导管癌患者中,研究了血液免疫细胞、肿瘤及其微环境中自发和多克隆激活剂刺激的细胞因子产生情况。采用固相酶联免疫吸附测定法测定白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、白细胞介素-17(IL-17)、白细胞介素-18(IL-18)、白细胞介素-1β(IL-1β)、白细胞介素-1受体拮抗剂(IL-1Ra)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、粒细胞集落刺激因子(G-CSF)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、血管内皮生长因子(VEGF)和单核细胞趋化蛋白-1(MCP-1)的浓度。在细胞外基质研究过程中,评估了纤维成分的状况以及中性糖蛋白和硫酸化糖胺聚糖的存在情况。95例患者中有35例检测到区域淋巴结转移。结果表明,无论有无淋巴结转移,多克隆激活剂对血液免疫细胞产生细胞因子的影响指数,对于IL-6、IL-8和IL-1β是不同的;而对于肿瘤及其微环境产生细胞因子的情况,多克隆激活剂对IL-2和IL-17的影响指数是不同的。淋巴结转移的存在与细胞因子自发产生的增加相对应,而无淋巴结转移则与多克隆激活剂刺激的细胞因子产生增加相对应。多克隆激活剂对血液免疫细胞产生细胞因子的影响指数值表明多克隆激活剂具有高度刺激作用,而多克隆激活剂对肿瘤及其微环境产生细胞因子的影响指数值表明多克隆激活剂的作用较低,有时甚至没有作用。基于这些数据,我们提出了多克隆激活剂影响指数的比值,以便更好地评估术前淋巴转移的可能性。在对细胞外基质进行表征后,我们发现了一个临界点,在100%的情况下,根据细胞外基质的状况可以预测淋巴结转移的存在。利用所获得的数据,我们为检查时无淋巴结转移的女性提出了一个转移风险组。