Tumor-associated macrophages promote tumor metastasis via the TGF-β/SOX9 axis in non-small cell lung cancer

• Published in: Oncotarget Vol. 8; no. 59; pp. 99801 - 99815
• Main Authors: Zhang, Shuai, Che, Dehai, Yang, Fang, Chi, Chunling, Meng, Hongxue, Shen, Jing, Qi, Li, Liu, Fang, Lv, Liyan, Li, Yue, Meng, Qingwei, Liu, Junning, Shang, Lihua, Yu, Yan
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 21.11.2017
• Subjects: Research Paper; TGF-β; SOX9; metastasis; non-small cell lung cancer (NSCLC); tumor-associated macrophages (TAMs)
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.21068

Tumor-associated macrophages (TAMs), most of which display the immunosuppressive M2 phenotype, affect the tumor microenvironment and promote progression and metastasis in lung carcinoma. In this study, we analyzed clinical non-small cell lung cancer (NSCLC) samples and found that high densities of TAMs were associated with a poor prognosis in NSCLC patients. Moreover, the number of TAMs present correlated positively with expression of sex determining region Y (SRY)-related high mobility group box 9 (SOX9) in NSCLC tissues. TAMs secreted TGF-β, which increased SOX9 expression and promoted epithelial-to-mesenchymal transition (EMT) in lung cancer cells, thereby promoting tumor proliferation, migration, and invasion. SOX9 knockdown inhibited EMT, indicating that TGF-β-mediated EMT is SOX9-dependent. TGF-β induced SOX9 expression by upregulating the C-jun/SMAD3 pathway. These results indicate that TGF-β secreted by TAMs promotes SOX9 expression via the C-jun/SMAD3 pathway, thereby promoting tumor metastasis. The TGF-β/SOX9 axis may therefore be an effective target for the treatment of lung cancer.