VEGF-R2 and TNF-R1 expression and cytokine production by samples ofmammary adenocarcinomas and correlations with histopathological parameters ofthese malignant tumors

摘要

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 KVEGF-R2/VEGF-A and KTNF-R1/TNF-α 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 thesame MAC samples. A direct correlation was identified betweenKVEGF-R/VEGF-A and some histopathological MAC characteristics:proportion of cells undergoing mitosis or pathological mitosis in MAC and poorlydifferentiated cells. KVEGF-R2/VEGF-A directly correlated with theconcentration in supernatant interleukin (IL)-18 and interferon (IFN)-γ.KTNF-R1/TNF-α was inversely correlated with the concentration insupernatant of IL-1Ra, IL-8, and granulocyte-macrophage colony-stimulatingfactor (GM-CSF). The data obtained show that the high-level production of IL-18and IL-1β by MAC, overexpression of VEGF-R2 in tumor (at relatively low VEGF-Aproduction), and the high level of IFN-γ production are attributed factorscontributing to the formation of a population of low-grade cells in the tumor.The factors regulating the population of moderately differentiated cells in thetumor are referred to as IL-1Ra, IL-8, and GM-CSF.