Tuberculous pleural effusion-induced Arg-1⁺ macrophage polarization contributes to lung cancer progression via autophagy signaling

초록

Background The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (M & Fcy;) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1(+) M & Fcy; in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. Methods The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1(+) M & Fcy; and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Gu & eacute;rin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion. Results Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1(+) M & Fcy; polarization of murine bone marrow-derived M & Fcy;. TPE-induced M2 Arg-1(+) M & Fcy; polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1(+) M & Fcy; both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression. Conclusion Tuberculous pleural fibrosis induces M2 Arg-1(+) polarization, and M2 Arg-1(+) M & Fcy; contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1(+) tumor associated M & Fcy; may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.

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