Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer

Posted on 03.06.2020 - 03:37
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.


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Lu, Chia-Sing; Shiau, Ai-Li; Su, Bing-Hua; Hsu, Tsui-Shan; Wang, Chung-Teng; Su, Yu-Chu; et al. (2020): Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5003873.v1


Journal of Hematology & Oncology


Chia-Sing Lu
Ai-Li Shiau
Bing-Hua Su
Tsui-Shan Hsu
Chung-Teng Wang
Yu-Chu Su
Ming-Shian Tsai
Yin-Hsun Feng
Yau-Lin Tseng
Yi-Ting Yen
Chao-Liang Wu
Gia-Shing Shieh
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