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Fucoidan reduced the invasion of oral squamous cell carcinoma cells and modified their effects to macrophages

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Abstract

Fucoidan is a complex of polysaccharides showing antitumor and immunomodulation properties. Our previous studies found its regulation to myeloid immune cells, including macrophages. Aberrant infiltration and functions of macrophages are commonly found in oral squamous cell carcinoma (OSCC). In this study, we analyzed the effects of fucoidan on invasion of OSCC cells, and their regulation to macrophages, trying to evaluate its role as a potential therapy for OSCC. CAL27 and THP-1-derived macrophages were used as models for OSCC cells and tumor-infiltrated macrophages in the in vitro study, respectively. The effects of fucoidan on invasion of OSCC cells and their recruitment to macrophages were analyzed by transwell assay. KIF4A siRNA transfection was performed to investigate its role in fucoidan-modulated OSCC cells invasion. CCL3-neutralizing antibody was added into the conditioned medium of OSCC cells to evaluate its role in fucoidan-mediated macrophages recruitment and re-education. Fucoidan reduced the invasive potential of CAL27 cells with a decrease of MMP-2 and KIF4A transcription. KIF4A knockdown in CAL27 cells led to decreased invasion and MMP-2 expression. The conditioned medium of fucoidan-treated CAL27 cells promoted recruitment and inflammatory cytokines secretion on THP-1-derived macrophages. Further analysis found that fucoidan increased CCL3 production in CAL27 cells. Blocking CCL3 expression reversed the effects of fucoidan on macrophage recruitment and re-education. Our study found that fucoidan regulated the invasion of OSCC cells and also their recruiting and re-educating effects on macrophages, suggesting it could be a complementary approach in the treatment of OSCC.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81271105, 31470885 and 31270971).

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    Authors and Affiliations

    1. Department of Oral and Maxillofacial Surgery and Institution of Dental Medicine, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People’s Republic of China

      Junda Lin, Ketao Wang, Yijun Luan, Yan Xu, Xiaobin Song, Wanye Tan, Shaohua Liu, Fengcai Wei & Xun Qu

    2. Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People’s Republic of China

      Huayang Wang, Qianqian Shao & Xun Qu

    3. Key Laboratory of Precision Biomedicine, Institutes of Zhongyuan Biomedical Sciences, Liaocheng People’s Hospital, 67 Dongchangxi Road, Liaocheng, 252000, Shandong, People’s Republic of China

      Fengcai Wei & Xun Qu

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    1. Junda Lin
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    Junda Lin and Ketao Wang have contributed equally to this work.

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    Lin, J., Wang, K., Wang, H. et al. Fucoidan reduced the invasion of oral squamous cell carcinoma cells and modified their effects to macrophages. Med Oncol 34, 9 (2017). https://doi.org/10.1007/s12032-016-0858-1

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