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

Autor: Yu-ichiro Koma, Hiroshi Yokozaki, Noriaki Arai, Yoshihiro Kakeji, Manabu Shigeoka, Nobuhisa Takase, Naoki Urakawa, Hiroaki Akiyama, Mari Nishio
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Cancer Research
Pathology
Esophageal Neoplasms
Macrophage
Esophageal cancer
FGF-2
Fibroblast growth factor
0302 clinical medicine
Cell Movement
Medicine
NCAM
Neural Cell Adhesion Molecules
Middle Aged
Phenotype
Tumor microenvironment
Oncology
030220 oncology & carcinogenesis
CYR61
Carcinoma
Squamous Cell
Female
Fibroblast Growth Factor 2
RNA Interference
Esophageal Squamous Cell Carcinoma
Signal Transduction
Macrophage colony-stimulating factor
medicine.medical_specialty
Stromal cell
Cell Survival
Tumor-associated macrophage
Transfection
03 medical and health sciences
Cell Line
Tumor
Paracrine Communication
Humans
Receptor
Fibroblast Growth Factor
Type 1
Aged
business.industry
Macrophages
Fibroblast growth factor receptor 1
FGFR1
030104 developmental biology
Culture Media
Conditioned
Cancer research
Neural cell adhesion molecule
Phosphatidylinositol 3-Kinase
Stromal Cells
business
Proto-Oncogene Proteins c-akt
Zdroj: Cancer Letters. 380:47-58
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2016.06.009
Popis: 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.
Databáze: OpenAIRE
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