title: Fucoidan reduced the invasion of oral squamous cell carcinoma cells and modified their effects to macrophages.
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.
authors.affiliation: 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.
authors.forename: Junda
authors.initials: J
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Ketao
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Huayang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Luan
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Wanye
authors.initials: W
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Liu
authors.affiliation: 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. weifc1949@163.com.|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. weifc1949@163.com.
authors.forename: Fengcai
authors.initials: F
authors.lastname: Wei
authors.affiliation: 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. quxun@sdu.edu.cn.|Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China. quxun@sdu.edu.cn.|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. quxun@sdu.edu.cn.
authors.forename: Xun
authors.identifier: http://orcid.org/0000-0001-7057-5975
authors.initials: X
authors.lastname: Qu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D054405:Chemokine CCL3 / Q000096:biosynthesis; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016547:Kinesins / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009361:Neoplasm Invasiveness; D011134:Polysaccharides / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D011134:Polysaccharides; C007789:fucoidan; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C484228:KIF4A protein, human; D016547:Kinesins
keywords: Fucoidan; Invasion; Macrophage; Oral squamous cell carcinoma; Recruitment