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- Title
Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer.
- Authors
Lu, Chia-Sing; Shiau, Ai-Li; Su, Bing-Hua; Hsu, Tsui-Shan; Wang, Chung-Teng; Su, Yu-Chu; Tsai, Ming-Shian; Feng, Yin-Hsun; Tseng, Yau-Lin; Yen, Yi-Ting; Wu, Chao-Liang; Shieh, Gia-Shing
- Abstract
Background: Expression of Oct4 maintains cancer stem cell (CSC)-like properties in lung cancer cells and is correlated with poor prognosis of lung adenocarcinoma. M2-type tumor-associated macrophages (TAMs) promote cancer cell migration and metastasis. Tumor microenvironments promote monocyte differentiation into M2 TAMs via a complex cytokine-based connection. We explored the role of Oct4 in cytokine secretion in lung cancer and its impact on M2 TAM polarization. Methods: Monocytes co-cultured with the conditioned medium from Oct4-overexpressing lung cancer cells were used to investigate M2 TAM differentiation. The inflammatory factors in the conditioned medium of Oct4-overexpressing A549 cells were examined using human inflammation antibody arrays. The correlations of Oct4, macrophage colony-stimulating factor (M-CSF), and M2 TAMs were validated in lung cancer cells, syngeneic mouse lung tumor models, and clinical samples of non-small cell lung cancer (NSCLC). Results: Oct4-overexpressing A549 cells expressed elevated levels of M-CSF, which contributed to increased M2 macrophages and enhanced tumor migration. Overexpression of Oct4 enhanced tumor growth and reduced the survival of lung tumor-bearing mice, which was correlated with increased number of M2 macrophages in lung cancer. Notably, NSCLC patients with high expression levels of Oct4, M-CSF, and M2 TAMs had the poorest recurrence-free survival. A positive correlation between Oct4, M-CSF, and M2 TAMs was observed in the tumor tissue of NSCLC patient. Treatment with all-trans retinoic acid exerted anti-tumor effects and reduced M2 TAMs in tumor-bearing mice. Conclusions: Our results indicate that Oct4 expressed by lung cancer cells promotes M2 macrophage polarization through upregulation of M-CSF secretion, leading to cancer growth and metastasis. Our findings also implicate that the Oct4/M-CSF axis in M2 macrophage polarization may be potential therapeutic targets for lung cancer.
- Subjects
MACROPHAGE colony-stimulating factor; LUNG cancer; NON-small-cell lung carcinoma; CANCER stem cells; CANCER cell migration
- Publication
Journal of Hematology & Oncology, 2020, Vol 13, Issue 1, p1
- ISSN
1756-8722
- Publication type
Article
- DOI
10.1186/s13045-020-00887-1