Abstract
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 (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1(+) MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1(+) MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin 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(+) MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1(+) MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1(+) MФ 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(+) MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1(+) tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.