1 Novosibirsk State Medical University, Novosibirsk, Russia.
2 Institute of Molecular Biology and Biophysics, Subdivision of Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia.
Int J Immunopathol Pharmacol. 2018 Jan-Dec;32:2058738418787990. doi: 10.1177/2058738418787990.
Currently, the role of cytokines in the tumor progression, including breast cancer, is universally recognized. At the same time, there are still many questions concerning the role of individual cytokines and receptors for cytokines in various morphogenetic processes underlying the tumor progression. The objective of this work was to study cytokine production and vascular endothelial growth factor (VEGF)-R2 and VEGF-R1 expression by mammary adenocarcinoma (MAC) and the correlations with histopathological parameters of malignant tumors. The object of the study was cultured tumor biopsy samples from 47 women aged 43-75 years with invasive ductal carcinoma, which was classified as grade II-III adenocarcinoma. It was shown that the cytokine profiles of the supernatants of MAC samples from patients differ greatly. A correlation between the levels of VEGF-R2 and tumor necrosis factor (TNF)-R1 expression was observed. Correlations were also revealed during analysis of the relations of histopathological MAC indicators with K and K coefficients, which are equal, respectively, to the ratio of expression values of receptors VEGF-R2 and TNF-R1 to the concentrations of the relevant cytokines (VEGF-A and TNF-α) in the culture supernatants of the same MAC samples. A direct correlation was identified between K and some histopathological MAC characteristics: proportion of cells undergoing mitosis or pathological mitosis in MAC and poorly differentiated cells. K directly correlated with the concentration in supernatant interleukin (IL)-18 and interferon (IFN)-γ. K was inversely correlated with the concentration in supernatant of IL-1Ra, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The data obtained show that the high-level production of IL-18 and IL-1β by MAC, overexpression of VEGF-R2 in tumor (at relatively low VEGF-A production), and the high level of IFN-γ production are attributed factors contributing to the formation of a population of low-grade cells in the tumor. The factors regulating the population of moderately differentiated cells in the tumor are referred to as IL-1Ra, IL-8, and GM-CSF.
目前，细胞因子在肿瘤进展中的作用，包括乳腺癌，已得到普遍认可。同时，对于细胞因子的个体作用以及细胞因子受体在肿瘤进展中各种形态发生过程中的作用，仍有许多问题尚未解决。本工作旨在研究乳腺癌的细胞因子产生和血管内皮生长因子（VEGF）-R2 和 VEGF-R1 的表达，并与恶性肿瘤的组织病理学参数相关。研究对象为 47 名年龄 43-75 岁的浸润性导管癌患者的培养肿瘤活检样本，这些患者被归类为 II-III 级腺癌。结果表明，患者 MAC 样本上清液中的细胞因子谱差异很大。观察到 VEGF-R2 水平与肿瘤坏死因子（TNF）-R1 表达之间存在相关性。在分析 MAC 组织病理学指标与 K 和 K'系数的关系时也揭示了相关性，这两个系数分别等于 VEGF-R2 和 TNF-R1 受体表达值与同一 MAC 样本培养上清液中相关细胞因子（VEGF-A 和 TNF-α）浓度的比值。K 与某些 MAC 组织病理学特征之间存在直接相关性：MAC 中细胞有丝分裂或病理性有丝分裂的比例和低分化细胞。K 与上清液中白细胞介素（IL）-18 和干扰素（IFN）-γ的浓度直接相关。K 与上清液中 IL-1Ra、IL-8 和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的浓度呈负相关。所得数据表明，MAC 高水平产生 IL-18 和 IL-1β，肿瘤中 VEGF-R2 过表达（在相对较低的 VEGF-A 产生情况下），以及高水平 IFN-γ 的产生是肿瘤中低级别细胞群形成的促成因素。调节肿瘤中中等分化细胞群的因素被认为是 IL-1Ra、IL-8 和 GM-CSF。
