Abstract
Purpose
The presence of M2 macrophages within primary tumors has been correlated with a poor prognosis for many types of cancer. However, little is known about the role of M2 macrophages in gallbladder cancer (GBC).
Methods
The number of M2 macrophages in 78 GBC and 16 normal gallbladder tissue samples was assessed by immunohistochemistry. The THP-1 monocyte cell line was differentiated into M2 macrophages and co-cultured with GBC-derived cell lines. The effect of M2 macrophages on promoting GBC cell migration and invasion was analyzed using migration, invasion and scratch wound healing assays. Western blotting and real-time PCR were used to assess the expression of epithelial-mesenchymal transition (EMT) markers and the activation status of the PI3K/Akt signaling pathway in GBC cells co-cultured with THP-1-derived macrophages.
Results
The average number of M2 macrophages was found to be significantly higher in GBC tissues than in normal gallbladder tissues. We also found that GBC patients with higher M2 macrophage counts exhibited poorer overall survival rates. Co-culture with M2 macrophages significantly promoted the migration, invasion and EMT of GBC cells. Moreover, we found that CCL18 secreted from M2 macrophages had the same effect on GBC cells as M2 macrophages. Blocking the function of CCL18 with a neutralizing antibody reversed this effect. Finally, we found that M2 macrophages could activate PI3K/Akt signaling in GBC cells, thereby leading to migration, invasion and EMT of these cells.
Conclusions
Our findings contribute to our understanding of the role of chronic inflammation in GBC development and progression, and may offer potential therapeutic targets for GBC.
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Change history
01 September 2022
A Correction to this paper has been published: https://doi.org/10.1007/s13402-022-00679-4
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Acknowledgments
This work was partially supported by the National Natural Science Foundation of China (Grant No. 81672405), the Key Project of the Natural Science Foundation of Guangdong Province, China (Grant No. 4210016041), the Science and Technology Program of Guangzhou, China (Grant No. 4250016043), a grant from the Guangdong Science and Technology Department (2015B050501004), Grant [2013] 163 from the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of the Guangzhou Bureau of Science and Information Technology, and Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of the Guangdong Higher Education Institutes. We thank Pro. Dong Yin from Sun Yat-Sen Memorial Hospital and Dr. Hui Shen from Renji Hospital, School of Medicine, Shanghai Jiao Tong University, for their technical support and Dr. Jing Wei and Fang Su from Sun Yat-Sen Memorial Hospital for conducting the flow cytometry experiments.
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The original version of this article was revised: In this article Figures 2b, 3c, 3e, 4a-4c, 5c, and 5d were incorrect. The original article has been corrected.
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Zhou, Z., Peng, Y., Wu, X. et al. CCL18 secreted from M2 macrophages promotes migration and invasion via the PI3K/Akt pathway in gallbladder cancer. Cell Oncol. 42, 81–92 (2019). https://doi.org/10.1007/s13402-018-0410-8
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DOI: https://doi.org/10.1007/s13402-018-0410-8