Macrophage ERα promoted invasion of endometrial cancer cell by mTOR/KIF5B-mediated epithelial to mesenchymal transition.

Abstract

Tumor-associated macrophages (TAMs) exert tumor-promoting effects. There have been reports that estrogen receptors (ERs) are expressed on the infiltrating macrophages of endometriosis, ovarian cancer and lung cancer. However, the role of ERs in macrophages is not well characterized. In this study, we identified that ER alpha (ERα) expression on the macrophages of human endometrial cancer was positively correlated with cancer progression. Conditioned medium from selective ERα agonist-treated M2 macrophages induced the epithelial to mesenchymal transition (EMT) in endometrial cancer cells. However, this effect can be inhibited by ERα antagonist. Here, we showed that macrophages ERα-engaged abundantly produced chemokine (C-C motif) ligand 18 (CCL18), and its expression promoted the invasion of endometrial cancer cells by activating the extracellular signal-regulated kinase 1/2 pathway, whereas suppressing CCL18 abrogated these effects. Furthermore, we identified that CCL18 derived from TAMs upregulated KIF5B expression to promote EMT via activating the PI3K/AKT/mTOR signaling pathway in endometrial cancer. Overall, our findings show how ERα-engaged infiltrating macrophages initiate chronic inflammation and promote the aggressive progression of endometrial cancer cells. ERα-positive TAMs act as drivers of endometrial cancer, which may become a potential therapeutic target.

• Authors: Xuanxuan Jing, Jin Peng, Yu Dou, Jintang Sun, Chao Ma, Qingjie Wang, Lin Zhang, Xia Luo, Beihua Kong, Yun Zhang, Lijie Wang, Xun Qu
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 97 Issue 6 Pg. 563-576 (07 2019) ISSN: 1440-1711 [Electronic] United States
• PMID: 30779215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Australasian Society for Immunology Inc.

Chemical References

• CCL18 protein, human
• Chemokines, CC
• Estrogen Receptor alpha
• KIF5B protein, human
• TOR Serine-Threonine Kinases
• Kinesins

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Chemokines, CC (metabolism)
• Endometrial Neoplasms (immunology, pathology)
• Epithelial-Mesenchymal Transition (immunology)
• Estrogen Receptor alpha (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kinesins (genetics, metabolism)
• Macrophages (immunology)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)