Roles of IL-7R Induced by Interactions between Cancer Cells and Macrophages in the Progression of Esophageal Squamous Cell Carcinoma.
Roles of IL-7R Induced by Interactions between Cancer Cells and Macrophages in the Progression of Esophageal Squamous Cell Carcinoma.
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癌细胞与巨噬细胞之间相互作用在食管鳞状细胞癌的进展中引起的IL-7R的作用。
作者：
肿瘤相关巨噬细胞(TAMs)在多种癌症的发生发展中起着重要作用。我们先前曾报道，在食管鳞癌组织中的浸润密度与食管鳞癌患者的不良预后有关。为了阐明ESCC微环境中直接相互作用的意义，我们先前建立了ESCC细胞和巨噬细胞的直接共培养实验。在本研究中，ESCC细胞与巨噬细胞直接共培养可诱导ESCC表达白介素7受体(IL7R)。IL-7R过表达通过激活Akt和ERK1/2信号通路促进ESCC细胞的存活和生长。此外，IL-7/IL-7R轴通过Akt和ERK1/2信号通路促进ESCC细胞迁移。癌巢中IL-7R高表达的ESCC患者的无病生存率较低。IL-7R可能成为食管癌治疗的新靶点。肿瘤相关巨噬细胞(TAMs)的高侵袭与食管鳞癌(ESCC)的不良预后密切相关，TAMs在多种癌症的发生发展中起重要作用。除了先前报道的迁移和侵袭增加外，直接与巨噬细胞共培养的ESCC细胞显示出更强的存活和生长能力。此外，白介素类相关分子与食管鳞癌有关；然而，这种联系背后的确切机制尚不清楚。因此，我们探讨了白介素类相关分子在食管鳞癌进展中的作用。对单独培养和联合培养的ESCC细胞进行的基因芯片分析表明，在与巨噬细胞共同培养的ESCC细胞中，IL-7R表达上调。IL-7R过表达通过激活Akt和ERK1/2信号通路促进ESCC细胞的存活和生长。IL-7/IL-7R轴也通过Akt和ERK1/2信号通路促进ESCC细胞迁移。免疫组织化学结果显示，癌巢中IL-7R高表达的ESCC患者的无瘤生存率有下降趋势，并与肿瘤相关的成纤维细胞和巨噬细胞的数量增加密切相关。因此，IL-7R在与巨噬细胞直接共培养时上调，可能通过促进癌细胞中各种恶性表型的发展而促进ESCC的进展。
Tumor-associated macrophages (TAMs) play significant roles in the progression of numerous types of cancers. We previously reported that the density of TAM infiltration in esophageal squamous cell carcinoma (ESCC) tissues is correlated with poor prognosis in patients with ESCC. To elucidate the significance of the direct interaction in the ESCC microenvironment, we previously established a direct co-culture assay of ESCC cells and macrophages. In the present study, direct co-culture of ESCC cells with macrophages induced interleukin 7 receptor (IL-7R) expression in ESCC. IL-7R overexpression promoted ESCC cell survival and growth via the activation of the Akt and Erk1/2 signaling pathways. Additionally, the IL-7/IL-7R axis promoted ESCC cell migration via the Akt and Erk1/2 signaling pathways. ESCC patients with high IL-7R expression in cancer nests exhibited poor disease-free survival. IL-7R could be a novel therapeutic target for ESCC. High infiltration of tumor-associated macrophages (TAMs), which contribute to the progression of several cancer types, is correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). In addition to the previously reported increase in migration and invasion, ESCC cells co-cultured directly with macrophages exhibited enhanced survival and growth. Furthermore, interleukin-related molecules are associated with ESCC; however, the precise mechanism underlying this association is unclear. Therefore, we explored the role of interleukin-related molecules in ESCC progression. A cDNA microarray analysis of monocultured and co-cultured ESCC cells revealed that the interleukin 7 receptor (IL-7R) was upregulated in ESCC cells co-cultured with macrophages. Overexpression of IL-7R promoted the survival and growth of ESCC cells by activating the Akt and Erk1/2 signaling pathways. The IL-7/IL-7R axis also contributed to the promotion of ESCC cell migration via the Akt and Erk1/2 signaling pathways. Furthermore, immunohistochemistry showed that ESCC patients with high IL-7R expression in cancer nests exhibited a trend toward poor prognosis in terms of disease-free survival, and showed significant correlation with increased numbers of infiltrating macrophages and cancer-associated fibroblasts. Therefore, IL-7R, which is upregulated when directly co-cultured with macrophages, may contribute to ESCC progression by promoting the development of various malignant phenotypes in cancer cells.
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