ANXA10 induction by interaction with tumor-associated macrophages promotes the growth of esophageal squamous cell carcinoma
ANXA10 induction by interaction with tumor-associated macrophages promotes the growth of esophageal squamous cell carcinoma
复制标题
DOI：
10.1111/pin.12771
复制
发表时间：
2019-03-01
影响因子：
2.2
通讯作者：
Yokozaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Kodaira, Himiko;Koma, Yu-ichiro;Yokozaki, Hiroshi
肿瘤相关巨噬细胞（TAM）在各种肿瘤的生长、血管生成和进展中发挥重要作用。尽管我们已经证明浸润性CD204(+) TAM数量增加与食管鳞状细胞癌(ESCC)预后不良有关，但TAM在食管鳞状细胞癌中的作用仍不清楚。在这里，为了研究 TAM 对 ESCC 肿瘤微环境的影响，我们使用人 ESCC 细胞系和 TAM 样外周血单核细胞衍生的巨噬细胞建立了共培养测定，并对单一培养和共培养 ESCC 细胞系进行了 cDNA 微阵列分析。我们的qRT-PCR证实，在共培养的ESCC细胞系中，CYP1A1、DHRS3、ANXA10、KLK6和CYP1B1 mRNA高度上调； AMTN 和 IGFL1 mRNA 下调。我们观察到钙依赖性磷脂结合蛋白 ANXA10 的高表达与侵袭深度、大量浸润 CD68+ 和 CD204+ TAM 以及较差的无病生存率密切相关 (P = 0.0216)。我们还发现 ANXA10 在体外通过 Akt 和 Erk1/2 通路的磷酸化促进 ESCC 细胞系的细胞生长。这些结果表明，在肿瘤微环境中与 TAM 相互作用诱导的 ANXA10 与人类 ESCC 组织中的细胞生长和不良预后相关。
Tumor-associated macrophages (TAMs) have important roles in the growth, angiogenesis and progression of various tumors. Although we have demonstrated the association of an increased number of infiltrating CD204(+) TAMs with poor prognosis in esophageal squamous cell carcinomas (ESCCs), the roles of TAMs in ESCC remain unclear. Here, to study the effects of TAMs on the tumor microenvironment of ESCCs, we established a co-culture assay using a human ESCC cell line and TAM-like peripheral blood monocyte-derived macrophages and performed a cDNA microarray analysis between monocultured and co-cultured ESCC cell lines. Our qRT-PCR confirmed that in the co-cultured ESCC cell lines, CYP1A1, DHRS3, ANXA10, KLK6 and CYP1B1 mRNA were highly up-regulated; AMTN and IGFL1 mRNA were down-regulated. We observed that the high expression of a calcium-dependent phospholipid-binding protein ANXA10 was closely associated with the depth of invasion and high numbers of infiltrating CD68(+) and CD204(+) TAMs and poor disease-free survival (P = 0.0216). We also found ANXA10 promoted the cell growth of ESCC cell lines via the phosphorylation of Akt and Erk1/2 pathways in vitro. These results suggest that ANXA10 induced by the interaction with TAMs in the tumor microenvironment is associated with cell growth and poor prognosis in human ESCC tissues.