O9 M1 macrophages evoke an increase in PIGR expression in MDA-MB468 breast cancer cells through interlukin-1β

Abstract

Abstract Introduction The polymeric immunoglobulin receptor (PIGR) is a transmembrane protein, which transports polymeric immunoglobulin (pIg) across the epithelial cells. High expression of PIGR in breast cancer has been reported to associate with increased 5-year survival rate. In this study, the factors in tumour microenvironment which affected PIGR expression in breast cancer cell lines, were investigated. Method M1, M2 macrophage conditioned media (CM) and recombinant human cytokines were used to determine factors which increased PIGR expression in breast cancer cells. The level of PIGR expression in the cells and secreted PIGR free secretory component (SC) were evaluated by real time quantitative polymerase chain reaction and Western blotting. Results M1 macrophage CM induced a striking dose dependent increase in PIGR mRNA expression in MDA-MB468 cells, up to 20-fold in 100% CM. Interferon gamma (IFNγ) and interleukin (IL)-1β also increased PIGR expression in MDA-MB468 cells. However, IL-1β was demonstrated to increase in M1 macrophages, while IFNγ was not. The role of IL-1β secreted from M1 macrophages in increasing expression of PIGR was confirmed by IL-1 receptor blockade, indicating that IL-1β was the M1 macrophage cytokine that enhanced PIGR expression in breast cancer cells. Conclusions IL-1β was the M1 macrophage cytokine which enhanced PIGR expression in breast cancer cells. IFNγ was also shown to increase PIGR expression in the present study. These imply that elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumour associated immune cells. Take-home Message IL-1β secreted from M1 macrophage enhances PIGR expression in breast cancer cells. The elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumour associated immune cells.