IL-1β from M2 macrophages promotes migration and invasion of ESCC cells enhancing epithelial-mesenchymal transition and activating NF-κB signaling pathway.

Despite the phenotype has been established that M2 macrophages promotes the metastasis of ESCC, question still remains as to how the M2 macrophages facilitated metastasis of ESCC cells. To begin with, immunohistochemistry was performed to detect the expression of CD163, one typical surface marker of M2 macrophages in 90 paired ESCC and its normal controls after meta-analyzing the relevant studies regarding M2 macrophages in ESCC, confirming that infiltration of M2 macrophages was significantly linked with lymph node metastasis, T classification, and inferior overall survival of ESCC. To explore the mechanism behind, protein factors secreted by M2 macrophages were identified using antibody microarray. Six different significantly differential protein factors were screened out, including IL-1β, TIMP1, IL-1α, MDC, TGF-β1, and TGF-β2. Among which, IL-1β was picked up as cytokine as interest based on previous reports and its absolute fold. Functional analysis of IL-1β showed that IL-1β was able to promote migration and invasion of ESCC cells, enhancing epithelial-mesenchymal transition, and activating NF-κB pathway. Our study supports the promoting role of M2 macrophages in metastasis of ESCC cells, enriching the profile of protein factors released from M2 macrophages.