NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells. Issue 1 (28th September 2016)

• Record Type: Journal Article
• Authors: Takase, Nobuhisa; Koma, Yu-ichiro; Urakawa, Naoki; Nishio, Mari; Arai, Noriaki; Akiyama, Hiroaki; Shigeoka, Manabu; Kakeji, Yoshihiro; Yokozaki, Hiroshi
• Is Part Of: Cancer letters. Volume 380:Issue 1(2016)
• Page Start: 47
• Page End: 58
• Publication Date: 2016-09-28
• Subjects: NCAM -- FGF-2 -- FGFR1 -- Esophageal cancer -- Macrophage -- Tumor microenvironment; Ct threshold cycle -- Cyr61 cysteine-rich angiogenic inducer 61 -- DFS disease free survival -- DMEM Dulbecco's Modified Eagle's Medium -- ESCC esophageal squamous cell carcinoma -- FGF-2 fibroblast growth factor-2 -- FGFR1 fibroblast growth factor receptor 1 -- GDF15 growth differentiation factor 15 -- IL interleukin: Macrophage_L_THP-1, TPA-treated THP-1 macrophage-like cell -- Macrophage_L PBMo-derived macrophage-like cell -- M-CSF macrophage-colony stimulating factor -- MMP matrix metalloprotease -- NC negative control -- NCAM neural cell adhesion molecule -- OS overall survival -- PBMC peripheral blood mononuclear cell -- PBMo peripheral blood monocyte -- rhFGF-2 recombinant human FGF-2 -- TAM tumor-associated macrophage -- TAM_L Macrophage_L stimulated with TECM -- TAM_L_TE-9 Macrophage_L stimulated with TE-9CM -- TAM_L_THP-1 Macrophage_L_THP-1 stimulated with TECM -- TAM_L_THP-1_TE-9 Macrophage_L_THP-1 stimulated with TE-9CM -- TECM conditioned medium of the TE series ESCC cell line -- THP-1 a human acute monocytic leukemia cell line -- TPA 12-O-tetradecanoylphorbol-13-acetate -- VEGFA vascular endothelial growth factor A; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.06.009
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: NCAM expression in PBMo-derived macrophages is significantly up-regulated by TECM. Polarization of TAM promotes migration and survival through PI3K-Akt and FGFR1. NCAM is involved in TAM migration/survival through PI3K-Akt and FGFR1 signaling. FGF-2 promotes TAM and ESCC cell migration/survival through FGF-2/FGFR1. Up-regulated FGF-2 in stroma is associated with more aggressive ESCC phenotypes. Abstract: 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 (Macrophage_Ls) and Macrophage_Ls stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAM_Ls) using cDNA microarray analysis. Among the highly expressed genes in TAM_Ls, we focused on neural cell adhesion molecule ( NCAM ). NCAM knockdown in TAM_Ls 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 Macrophage_Ls. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAM_Ls 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.