Oncotarget

Research Papers:

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

Shuai Zhang, Dehai Che, Fang Yang, Chunling Chi, Hongxue Meng, Jing Shen, Li Qi, Fang Liu, Liyan Lv, Yue Li, Qingwei Meng, Junning Liu, Lihua Shang and Yan Yu _

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Oncotarget. 2017; 8:99801-99815. https://doi.org/10.18632/oncotarget.21068

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Abstract

Shuai Zhang1, Dehai Che1, Fang Yang1, Chunling Chi2, Hongxue Meng3, Jing Shen1, Li Qi4, Fang Liu1, Liyan Lv5, Yue Li1, Qingwei Meng1, Junning Liu6, Lihua Shang1 and Yan Yu1

1The Sixth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China

2Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China

3Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China

4Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

5Department of Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

6Department of Oncology, The First Affiliated Hospital of Qiqihar Medical College, Qiqihar, China

Correspondence to:

Yan Yu, email: yuyan@ems.hrbmu.edu.cn

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

Received: March 21, 2017     Accepted: July 25, 2017     Published: September 16, 2017

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.


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