Open Access

High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression

  • Authors:
    • Chong‑Yu Su
    • Xiao‑Long Fu
    • Wei Duan
    • Pei‑Wu Yu
    • Yong‑Liang Zhao
  • View Affiliations

  • Published online on: February 27, 2018     https://doi.org/10.3892/ol.2018.8119
  • Pages: 6217-6224
  • Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the potential role of cluster of differentiation CD68+ tumor‑associated macrophages (TAMs) induced by interleukin (IL)-6 in the progression of gastric cancer (GC) and patient prognosis. The expression levels of IL‑6 and CD68 were detected by immunohistochemical staining in 60 samples of tumor and non‑tumor gastric tissues. CD14+ monocytes were isolated from peripheral blood mononuclear cells and stimulated with macrophage colony stimulation factor (M‑CSF) and IL‑6, and the expression levels of IL‑10, IL‑12, vascular endothelial growth factor (VEGF)‑C and transforming growth factor (TGF)‑β were measured by reverse transcription polymerase chain reaction and ELISA. The GC MGC‑803 cell line was co‑cultured with monocytes stimulated by M‑CSF and IL‑6 and the invasion ability of the MGC‑803 was evaluated by Transwell analysis. The levels of STAT3, P‑STAT3 and interferon‑regulatory factor 4 (IRF4) in the monocytes stimulated by M‑CSF and IL‑6 were detected by western blotting. The results demonstrated that the frequencies of IL‑6+ macrophages (Mφs) and CD68+ Mφs were significantly higher in tumor regions compared with the corresponding non‑tumor regions of GC tissues. Kaplan‑Meier analysis revealed that the densities of tumor‑infiltrating CD68+ or IL‑6+ Mφs were inversely associated with the overall survival rates of the patients. In vitro, the expression levels of IL‑10, VEGF‑C and TGF‑β significantly increased in CD14+ monocytes subsequent to M‑CSF and IL‑6 stimulation. The invasion abilities of MGC‑803 were increased by the monocytes stimulated with M‑CSF and IL‑6. The levels of STAT3, P‑STAT3 and IRF4 proteins increased in the monocytes stimulated by M‑CSF and IL‑6. In conclusion, the results from the present study suggest that a high density of CD68+ TAMs predicts a poor prognosis in GC. IL‑6 may polarize the Mφs and promote tumor invasion through the IL-6/STAT3/IRF4 signaling pathway.
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May-2018
Volume 15 Issue 5

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Spandidos Publications style
Su CY, Fu XL, Duan W, Yu PW and Zhao YL: High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression. Oncol Lett 15: 6217-6224, 2018
APA
Su, C., Fu, X., Duan, W., Yu, P., & Zhao, Y. (2018). High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression. Oncology Letters, 15, 6217-6224. https://doi.org/10.3892/ol.2018.8119
MLA
Su, C., Fu, X., Duan, W., Yu, P., Zhao, Y."High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression". Oncology Letters 15.5 (2018): 6217-6224.
Chicago
Su, C., Fu, X., Duan, W., Yu, P., Zhao, Y."High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression". Oncology Letters 15, no. 5 (2018): 6217-6224. https://doi.org/10.3892/ol.2018.8119