Lin Junda, Wang Ketao, Wang Huayang, Shao Qianqian, Luan Yijun, Xu Yan, Song Xiaobin, Tan Wanye, Liu Shaohua, Wei Fengcai, Qu Xun
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.
Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China.
Med Oncol. 2017 Jan;34(1):9. doi: 10.1007/s12032-016-0858-1. Epub 2016 Dec 21.
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.
岩藻依聚糖是一种具有抗肿瘤和免疫调节特性的多糖复合物。我们之前的研究发现它对髓系免疫细胞有调节作用，包括巨噬细胞。巨噬细胞的异常浸润和功能在口腔鳞状细胞癌（OSCC）中普遍存在。在本研究中，我们分析了岩藻依聚糖对OSCC细胞侵袭的影响及其对巨噬细胞的调节作用，试图评估其作为OSCC潜在治疗方法的作用。在体外研究中，分别使用CAL27和THP-1来源的巨噬细胞作为OSCC细胞和肿瘤浸润巨噬细胞的模型。通过Transwell实验分析岩藻依聚糖对OSCC细胞侵袭及其向巨噬细胞募集的影响。进行KIF4A siRNA转染以研究其在岩藻依聚糖调节的OSCC细胞侵袭中的作用。将CCL3中和抗体添加到OSCC细胞的条件培养基中，以评估其在岩藻依聚糖介导的巨噬细胞募集和再教育中的作用。岩藻依聚糖降低了CAL27细胞的侵袭潜力，同时MMP-2和KIF4A转录水平降低。CAL27细胞中KIF4A基因敲低导致侵袭和MMP-2表达降低。经岩藻依聚糖处理的CAL27细胞的条件培养基促进了THP-1来源巨噬细胞的募集和炎性细胞因子分泌。进一步分析发现，岩藻依聚糖增加了CAL27细胞中CCL3的产生。阻断CCL3表达可逆转岩藻依聚糖对巨噬细胞募集和再教育的影响。我们的研究发现，岩藻依聚糖调节OSCC细胞的侵袭以及其对巨噬细胞的募集和再教育作用，表明它可能是治疗OSCC的一种补充方法。
