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

被引：63

作者：

Takase, Nobuhisa ^{[1
,2
]}

Koma, Yu-ichiro ^{[1
]}

Urakawa, Naoki ^{[1
,2
]}

Nishio, Mari ^{[1
]}

Arai, Noriaki ^{[1
]}

Akiyama, Hiroaki ^{[1
]}

Shigeoka, Manabu ^{[1
]}

Kakeji, Yoshihiro ^{[2
]}

Yokozaki, Hiroshi ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Div Pathol, Dept Pathol,Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan

[2] Kobe Univ, Grad Sch Med, Div Gastrointestinal Surg, Dept Surg,Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan

来源：

CANCER LETTERS | 2016年 / 380卷 / 01期

基金：

日本学术振兴会;

关键词：

NCAM; FGF-2; FGFR1; Esophageal cancer; Macrophage; Tumor microenvironment; FIBROBLAST-GROWTH-FACTOR; MOLECULE N-CAM; ADHESION MOLECULE; FACTOR RECEPTOR; PROGNOSTIC BIOMARKER; ACTIVATION; PROGRESSION; LUNG; EXPRESSION; CARCINOMA;

D O I：

10.1016/j.canlet.2016.06.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immuno-suppression 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 I (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 FGFRI signaling in the tumor microenvironment of ESCCs. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

引用

页码：47 / 58

页数：12

共 63 条

[1] Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies [J].