RRC ID 64535
Author Takase N, Koma Y, Urakawa N, Nishio M, Arai N, Akiyama H, Shigeoka M, Kakeji Y, Yokozaki H.
Title 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.
Journal Cancer Lett
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.
Volume 380(1)
Pages 47-58
Published 2016-9-28
DOI 10.1016/j.canlet.2016.06.009
PII S0304-3835(16)30369-X
PMID 27317650
MeSH Aged Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Movement* Cell Survival Culture Media, Conditioned / metabolism Esophageal Neoplasms / genetics Esophageal Neoplasms / metabolism* Esophageal Neoplasms / pathology Esophageal Squamous Cell Carcinoma Female Fibroblast Growth Factor 2 / metabolism* Humans Macrophages / metabolism* Macrophages / pathology Male Middle Aged Neural Cell Adhesion Molecules / genetics Neural Cell Adhesion Molecules / metabolism* Paracrine Communication Phenotype Phosphatidylinositol 3-Kinase / metabolism Proto-Oncogene Proteins c-akt / metabolism RNA Interference Receptor, Fibroblast Growth Factor, Type 1 / metabolism* Signal Transduction Stromal Cells / metabolism* Stromal Cells / pathology Transfection Tumor Microenvironment*
IF 7.36
Human and Animal Cells TE-8(RCB2098) TE-9(RCB1988) TE-15(RCB1951)