Rapamycin-induced M2 macrophage autophagy promotes the migration and invasion of bladder cancer cells via increased IL-10 secretion

• Published in: European journal of inflammation 2021, Vol.19
• Main Authors: Guo, Yuanyuan, Li, Zhong, Cao, Zhenxue, Ma, Tantu, Mei, Juan, Sun, Wei, Gao, Wuyue, Liu, Beibei, Liu, Jianmin, Wang, Rui
• Format: Article
• Language: English
• Subjects: Autophagy; Bladder cancer
• ISSN: 2058-7392; 1721-727X; 2058-7392
• DOI: 10.1177/20587392211049878

Intrduction: Rapamycin is an mTOR inhibitor and a prominent inducer of autophagy in cancer cells and tumor interstitial cells. Macrophages are the primary type of immune cells observed in the tumor microenvironment and serve varying roles in the progression of cancer by polarizing into distinct phenotypes. However, whether rapamycin-induced macrophage autophagy influences bladder cancer remains unclear. Methods: THP-1 cells were successfully polarized into M1 or M2 macrophages, which were identified by detecting CD86 (M1) or CD206 (M2) expressions using flow cytometry and measuring M1/M2-related mRNA expressions using reverse transcription-quantitative PCR. Rapamycin was employed for inducing autophagy, and then the influences of enhanced autophagic M1 and M2 macrophages on migration and invasion of bladder cancer cells were confirmed by wound healing and Transwell assay in the co-culture model. Furthermore, the gene and protein expressions of IL-10 and the underlying role are still unclear. Results: Rapamycin significantly increased autophagy levels in M1 and M2 macrophages, while only autophagy-enhanced M2 macrophages facilitated the migration and invasion of bladder cancer cells. Furthermore, rapamycin increased IL-10 secretion from M2 macrophages, which mediated the effects of M2 macrophages on migration and invasion of bladder cancer. Conclusion: Rapamycin induces M2 macrophage autophagy and promotes the migration and invasion of bladder cancer by increasing IL-10 secretion, suggesting that M2 macrophage autophagy is an underlying target of rapamycin in treating bladder cancer.