Cytokine Production by Blood Immune Cells, Tumor and its Microenvironment, Characteristics of Extracellular Matrix in Patients with Invasive Ductal Carcinoma of No Special Type

• Published in: Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Biomedical chemistry, 2020, Vol.14 (1), p.44-51
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Bioorganic Chemistry; Blood; Blood cells; Breast cancer; Breast carcinoma; Chemistry; Chemistry and Materials Science; Cytokines; Enzyme-linked immunosorbent assay; Extracellular matrix; Glycoproteins; Glycosaminoglycans; Granulocyte colony-stimulating factor; Granulocyte-macrophage colony-stimulating factor; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 10; Interleukin 17; Interleukin 18; Interleukin 2; Interleukin 4; Interleukin 6; Interleukin 8; Invasiveness; Lymph nodes; Lymphatic system; Medicinal Chemistry; Metastases; Metastasis; Monocyte chemoattractant protein 1; Polyclonal activators; Tumor cells; Vascular endothelial growth factor; γ-Interferon
• ISSN: 1990-7508; 1990-7516
• DOI: 10.1134/S1990750820010059

— The spontaneous and polyclonal activator-stimulated cytokine production by immunocompetent blood cells, the tumor and its microenvironment, as well as the state of the extracellular matrix were investigated in 95 patients with invasive breast carcinoma of no special type (IBC-NST) with lymphatic metastases. Concentrations 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 were determined by the ELISA method. Evaluation of extracellular matrix included the state of the fibrous component, the content of neutral glycoproteins and sulfated glycosaminoglycans. Regional lymph node metastases were found in 35 of 95 patients. The study showed that in the presence or absence of lymphogenous metastasis, the index of the influence of polyclonal activators (IPAI) on cytokine production by immunocompetent blood cells differed in three parameters (IL-6, IL-8 and IL-1β), while IPAI on the production of cytokines by tumor cells and its microenvironment differed in two (IL-2 and IL-17). The presence of lymphatic metastases corresponded to an increase in the spontaneous production of cytokines, while their absence corresponded to an increase in the production stimulated by polyclonal activators. The IAPI values on cytokine production by immunocompetent blood cells demonstrate the high stimulating effect of the polyclonal activators, while the IPAI values on cytokine production tumor cells and tumor microenvironment suggest low (if any) effect of polyclonal activators. Based on the data obtained, the ratio of the IPAI values is proposed for evaluation of probability of lymphatic metastases in the preoperative period. Evaluation of the extracellular matrix revealed a threshold, which in 100% of cases demonstrated the correspondence of the state of the extracellular matrix to the presence of metastases in the regional lymph nodes. Based on the results of this study, we proposed a risk group for metastasis among women lacking lymph nodes metastases at the time of the study.