Dataset Information

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

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.

SUBMITTER: Lu CS

PROVIDER: S-EPMC7268452 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Lu Chia-Sing CS Shiau Ai-Li AL Su Bing-Hua BH Hsu Tsui-Shan TS Wang Chung-Teng CT Su Yu-Chu YC Tsai Ming-Shian MS Feng Yin-Hsun YH Tseng Yau-Lin YL Yen Yi-Ting YT Wu Chao-Liang CL Shieh Gia-Shing GS

Journal of hematology & oncology 20200601 1

<h4>Background</h4>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.<h4>Methods</h4>Monocytes ...[more]

PMID: 32487125

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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