학술논문
Roles of IL-7R Induced by Interactions between Cancer Cells and Macrophages in the Progression of Esophageal Squamous Cell Carcinoma.
Document Type
Article
Author
Source
Subject
*DISEASE progression
*IN vitro studies
*REVERSE transcriptase polymerase chain reaction
*LOG-rank test
*IMMUNOHISTOCHEMISTRY
*MACROPHAGES
*PROGNOSIS
*T-test (Statistics)
*CHI-squared test
*KAPLAN-Meier estimator
*DESCRIPTIVE statistics
*ENZYME-linked immunosorbent assay
*CELL proliferation
*CELL lines
*DATA analysis software
*BIOLOGICAL assay
*SQUAMOUS cell carcinoma
*ESOPHAGEAL cancer
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Language
ISSN
2072-6694
Abstract
Simple Summary: 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. [ABSTRACT FROM AUTHOR]