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Oncotarget. 2017 Sep 16;8(59):99801-99815. doi: 10.18632/oncotarget.21068. eCollection 2017 Nov 21.

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

Author information

1
The Sixth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
2
Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
3
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
4
Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
5
Department of Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
6
Department of Oncology, The First Affiliated Hospital of Qiqihar Medical College, Qiqihar, China.

Abstract

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.

KEYWORDS:

SOX9; TGF-β; metastasis; non-small cell lung cancer (NSCLC); tumor-associated macrophages (TAMs)

Conflict of interest statement

CONFLICTS OF INTEREST The authors have no potential conflicts of interest to disclose.

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