Cancer Cell International (2020-12-01)

Intrahepatic cholangiocarcinoma induced M2-polarized tumor-associated macrophages facilitate tumor growth and invasiveness

  • Hui Yuan,
  • Zelong Lin,
  • Yingjun Liu,
  • Yuchuan Jiang,
  • Ke Liu,
  • Mengxian Tu,
  • Nan Yao,
  • Chen Qu,
  • Jian Hong

DOI
https://doi.org/10.1186/s12935-020-01687-w
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 14

Abstract

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Abstract Background M2-polarized tumor-associated macrophages (M2-TAMs) have been shown to correlate with the progression of various cancers, including intrahepatic cholangiocarcinoma (ICC). However, the interactions and mechanism between M2 macrophages and ICC are not completely clear. We aimed to clarify whether M2 macrophages promote the malignancy of ICC and its mechanism. Methods Two progressive murine models of ICC were used to evaluate the alterations in different macrophage populations and phenotypes. Furthermore, we assessed M2 macrophage infiltration in 48 human ICC and 15 normal liver samples. The protumor functions and the underlying molecular mechanisms of M2 macrophages in ICC were investigated in an in vitro coculture system. Results We found that the number of M2 macrophages was significantly higher in ICC tissues than in normal bile ducts in the two murine models. M2 macrophage infiltration was highly increased in peritumoral compared with intratumoral regions and normal liver (p < 0.01). ICC cells induced macrophages to differentiate into the M2-TAM phenotype, and coculture with these M2 macrophages promoted ICC cell proliferation, invasion and epithelial–mesenchymal transition (EMT) in vitro. Mechanistically, M2-TAM-derived IL-10 promoted the malignant properties of ICC cells through STAT3 signaling. Furthermore, blockade of IL-10/STAT3 signaling partly rescued the effects of M2 macrophages on ICC. Conclusion Our results indicated that M2-polarized macrophages induced by ICC promote tumor growth and invasiveness through IL-10/STAT3-induced EMT and might be a potential therapeutic target for ICC.

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