P64: Cytokine production by malignant and benign breast tumors

Abstract

Growing tumor and its microenvironment are capable to produce a number of cytokines that alter the nature of the antitumor surveillance by host immune system. Objective Comparative evaluation of cytokine-producing function of the invasive ductal carcinoma and fibroadenoma of the breast in vitro. Materials and methods Similar biopsies (V = 8 mm3) of the breast tumors were obtained using a special device, cultivated in DMEM F-12 at 37 °C for 72 h. Concentrations of the following cytokines: IL-1β, IL-1Ra, TNFα, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, VEGF and IFNγ in the supernatant of the tumor were measured with enzyme-linked immunosorbent assay (ELISA). Results The investigation of cytokines level in the supernatant of malignant and benign breast tumors revealed significant differences only in concentrations of IL-10, IL-17, IL-18 and IFNγ which had a contrary tendency. For example, the concentration of IL-10 was lower at invasive ductal carcinoma in comparison with fibroadenomas. The concentrations of IL-17, IL-18 and IFNγ at invasive ductal carcinoma were significantly higher than those of breast fibroadenomas. IL-17 and IL-18 are known to be pro-oncogenic cytokines, and the higher the level, the higher the severity of tumor progression. Reduction in the IL-10 concentration might be explained by the already formed neoplasm, which depends on angiogenesis. In this case, IL-10 no longer exerts antiangiogenic action, which contributes to tumor progression. Reduction in the IL-10 concentration, which inhibits the production of IFNγ leads to an increase in the IFNγ level. In early stages of tumor development, IFNγ provides an antitumor effect and at the same time facilitates the selection of a more malignant clones but its pro-tumoral action predominates at advanced stages of tumorigenesis. Moreover, higher concentration of IFNγ is supposed to be associated with biological effects of IL-18, which is its immediate inductor. In addition, malignant tumor cells are capable to produce their own IL-18, which stimulates tumor progression and facilitates the migration of endothelial cells involved in angiogenesis, which leads to intensified invasion and metastasis. Conclusion Cytokine production in supernatants of invasive ductal carcinoma compared with fibroadenoma of the breast is characterized by increase in IL-17, IL-18 and IFNγ concentrations and decrease in IL-10 concentration. Findings suggest the ability of malignant tumor and its microenvironment to secrete the pro-oncogenic cytokines. Fibroadenoma is also able to produce cytokines due to fibroblasts, fibrocytes and some leukocytes in its content.