Cytokine production in mammary adenocarcinoma and its microenvironmental cells in patients with or without metastases in regional lymph nodes

Abstract

In recent years, the concept of formation of a sufficiently autonomous cytokine network in a malignant tumour has emerged. In this regard, the data on the role of this network and its signalling pathways in the process of metastasis are an interesting topic. The aim of this study was to evaluate the in vitro cytokine-producing potential of mammary adenocarcinoma (MAC; and cells of its microenvironment) from patients with or without metastases in regional lymph nodes (LNs). By enzyme-linked immunosorbent assays of culture supernatants, we studied the cytokine production by biopsy samples of MAC: spontaneous and stimulated by polyclonal activators (PAs: phytohaemagglutinin, concanavalin A and lipopolysaccharide). The levels of spontaneous production of interleukin (IL)-10 and granulocyte colony-stimulating factor (G-CSF) and the amounts of IL-2, IL-10, G-CSF and monocyte chemoattractant protein-1 (MCP-1) produced during stimulation by PAs, as well as the index of stimulation by polyclonal activators (ISPA) for IL-2 production, were lower for MAC with LN metastasis than for MAC without LN metastasis. The levels of spontaneous production of IL-2 and interferon (IFN)-γ and the ISPA for granulocyte–macrophage colony-stimulating factor (GM-CSF) production were higher for MAC with LN metastasis. There were only three pairwise correlations between the produced cytokines that were specific to MAC with LN metastasis: IL-2 and IFN-γ, IL-6 and GM-CSF, and IL-8 and GM-CSF. There were 10 pairwise correlations between the produced cytokines that were specific to nonmetastasising MAC: IL-6 and IL-10, IL-6 and MCP-1, IL-8 and IL-10, IL-8 and MCP-1, IL-10 and G-CSF, IL-10 and MCP-1, IFN-γ and MCP-1, MCP-1 and G-CSF, G-CSF and IL-1Ra, and GM-CSF and tumour necrosis factor (TNF)-α. Our data indicate that metastatic tumours show desynchronisation of many pathways of induction and synthesis of cytokines that are characteristic of nonmetastatic tumours.