Novosibirsk State Medical University, Russia.
Institute of Molecular Biology and Biophysics, Subdivision of Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia.
Technol Cancer Res Treat. 2019 Jan-Dec;18:1533033819883626. doi: 10.1177/1533033819883626.
The aim of this study was to evaluate the relationship between cytokine production, GM-CSF receptor (CSF2RA), and IL-1 receptor (IL1R2) expression in mammary adenocarcinoma and their association with it histopathological parameters and lymph node metastasis.
We analyzed tumor biopsy samples (cultured ) from 50 women (aged 43-75) with invasive ductal mammary adenocarcinomas. Enzyme-linked immunosorbent assay method the concentrations of interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 17, interleukin 18, interleukin 1β, interleukin 1Ra, tumor necrosis factor α, interferon γ, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and vascular endothelial growth factor A were determined in culture supernatants. The expression of CSF2RA and IL1R2 in tumor biopsy was evaluated by immunohistochemical method.
We showed that the "cytokine profile" of a tumor (the ability of tumor cells and its microenvironment to produce different cytokines) is very individual. It has been shown that the features of the cytokine profile of the mammary adenocarcinoma are important for the formation and realization of the metastatic potential of the mammary adenocarcinoma. We found correlations between some histopathological parameters of mammary adenocarcinoma and coefficients K and K, which are the ratios of concentrations of granulocyte macrophage colony-stimulating factor and interleukin -1β to expression of CSF2RA and IL1R2, respectively. K positively correlated with highly differentiated cells, and K positively correlated with the number of mitoses, poorly differentiated cells, and a number of lymph nodes with metastases. K positively correlated with the concentrations of interleukin 6, interleukin 8, interleukin 1Ra, and granulocyte colony-stimulating factor. K positively correlated with concentrations of interleukin 1β and interferon γ and negative correlated with the concentrations of vascular endothelial growth factor A and tumor necrosis factor α. It is shown that K can be considered as a prognostic indicator predicting the probability of mammary adenocarcinoma metastasis to regional lymph nodes.
The ratios of granulocyte macrophage colony-stimulating factor and interleukin 1β cytokines, produced in tumor, to the expression of CSF2RA and IL1R2 depend on levels of interleukin 6, interleukin 8, tumor necrosis factor α, interferon γ, granulocyte colony-stimulating factor, and vascular endothelial growth factor A and are important factors affecting the progression and metastasis of the breast cancer.
本研究旨在评估乳腺腺癌中细胞因子产生、GM-CSF 受体（CSF2RA）和 IL-1 受体（IL1R2）表达之间的关系，及其与组织病理学参数和淋巴结转移的关系。
我们分析了 50 名患有浸润性导管乳腺癌的女性（年龄 43-75 岁）的肿瘤活检样本（培养）。采用酶联免疫吸附试验方法测定培养上清液中白细胞介素 2、白细胞介素 6、白细胞介素 8、白细胞介素 10、白细胞介素 17、白细胞介素 18、白细胞介素 1β、白细胞介素 1Ra、肿瘤坏死因子 α、干扰素 γ、粒细胞集落刺激因子、粒细胞-巨噬细胞集落刺激因子和血管内皮生长因子 A 的浓度。采用免疫组织化学方法评价肿瘤活检中 CSF2RA 和 IL1R2 的表达。
我们表明，肿瘤的“细胞因子谱”（肿瘤细胞及其微环境产生不同细胞因子的能力）非常个体化。已经表明，乳腺腺癌的细胞因子谱特征对于乳腺腺癌形成和实现转移潜能很重要。我们发现了一些乳腺腺癌的组织病理学参数与系数 K 和 K 之间的相关性，这些系数分别是粒细胞-巨噬细胞集落刺激因子和白细胞介素-1β与 CSF2RA 和 IL1R2 表达的比值。K 与高分化细胞呈正相关，而 K 与有丝分裂数、低分化细胞和有转移的淋巴结数呈正相关。K 与白细胞介素 6、白细胞介素 8、白细胞介素 1Ra 和粒细胞集落刺激因子的浓度呈正相关。K 与白细胞介素 1β和干扰素 γ的浓度呈正相关，与血管内皮生长因子 A 和肿瘤坏死因子 α 的浓度呈负相关。结果表明，K 可以被认为是预测乳腺腺癌向区域淋巴结转移概率的预后指标。
肿瘤中产生的粒细胞-巨噬细胞集落刺激因子和白细胞介素 1β细胞因子与 CSF2RA 和 IL1R2 表达的比值取决于白细胞介素 6、白细胞介素 8、肿瘤坏死因子 α、干扰素 γ、粒细胞集落刺激因子和血管内皮生长因子 A 的水平，是影响乳腺癌进展和转移的重要因素。
