Janus Kinase/Signal Converters, and the Transcriptional Activator Signaling Pathway Promotes Lung Cancer Through Increasing M2 Macrophage

Abstract

Accumulating evidence highlights the salient function of JAK/STAT signaling pathway in tumorigenesis and development. But the mechanism of JAK/STAT signaling in lung cancer remains elusive. This study assessed the impact of JAK/STAT on lung tumorigenesis and its interaction with microenvironment. Mouse model of primary lung cancer was established and then treated with JAK/STAT inhibitor. Immunofluorescence was performed to analyze fluorescent labels. Transwell assay determined the cell migration ability, and Western blot, immunohistochemistry, and immunofluorescence to detect the expression of JAK/STAT key proteins. Cell proliferation was measured by Kit-8 and colony formation. JAK/STAT key proteins were upregulated in lung cancer models. Inhibition of JAK/STAT led to a decrease in proliferative, migratory and invasive capability of lung cancer cells and macrophages from bone marrow and spleen. The cell invasion ability in the bone marrow and the proliferation of macrophages in the treatment group was weakened. When co-cultured with the treated macrophages, the proliferation of LLC1 cells was inhibited. Furthermore, in vitro flow cytometry indicated that JAK/STAT affected lung cancer progression by affecting the polarization of M1/M2 macrophages. Taken altogether, JAK/STAT signal enhances M2 macrophage expression and promotes lung cancer progression.