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Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immunosuppression of various cancers, including esophageal squamous cell carcinomas (ESCCs). To elucidate the roles of TAMs in ESCCs, we compared the gene expression profiles between human peripheral blood monocyte-derived macrophage-like cells (MacrophageLs) and MacrophageLs stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAMLs) using cDNA microarray analysis. Among the highly expressed genes in TAMLs, we focused on neural cell adhesion molecule (NCAM). NCAM knockdown in TAMLs revealed a significant decrease of migration and survival via a suppression of PI3K-Akt and fibroblast growth factor receptor 1 (FGFR1) signaling. Stimulation by TECM up-regulated the level of FGFR1 in MacrophageLs. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAMLs and TE-cells through FGFR1 signaling. Our immunohistochemical analysis of 70 surgically resected ESCC samples revealed that the up-regulated FGF-2 in stromal cells, including macrophages, was associated with more aggressive phenotypes and a high number of infiltrating M2 macrophages. These findings may indicate a novel role of NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of ESCCs.
Takase et al. (2016) studied this question.