title: Fucoidan inhibits CCL22 production through NF-κB pathway in M2 macrophages: a potential therapeutic strategy for cancer.
abstract: In tumor microenvironment, macrophages as a polarized M2 population promote tumor progression via releasing multiple cytokines and chemokines. A brown seaweed fucose-rich polysaccharide, fucoidan has antitumor activity and immune modulation through affecting tumor cells and lymphocytes. Here, we focused on the effect of fucoidan on macrophages especially M2 subtype. Our results demonstrated that fucoidan down-regulated partial cytokines and chemokines, especially a M2-type chemokine CCL22. Furthermore, fucoidan inhibited tumor cells migration and CD4+T lymphocytes, especially Treg cells, recruitment induced by M2 macrophages conditioned medium through suppression of CCL22. Mechanismly, fucoidan inhibited CCL22 via suppressing p65-NF-κB phosphorylation and nuclear translocation. In addition, p38-MAPK and PI3K-AKT also affected the expression of CCL22 through differential modulation of NF-κB transcriptional activity. Taken together, we reveal an interesting result that fucoidan can inhibit tumor cell migration and lymphocytes recruitment by suppressing CCL22 in M2 macrophages via NF-κB-dependent transcription, which may be a novel and promising mechanism for tumor immunotherapy.
authors: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.|Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Jia
authors: J
authors: Sun
authors: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Jintang
authors: J
authors: Sun
authors: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Bingfeng
authors: B
authors: Song
authors: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Lin
authors: L
authors: Zhang
authors: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Qianqian
authors: Q
authors: Shao
authors: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Yanguo
authors: Y
authors: Liu
authors: Key Laboratory of Precision Biomedicine, Institute of Zhongyuan Biomedical Sciences, Liaocheng People's hospital, Liaocheng, 252000, Shandong, P. R. China.
authors: Daoying
authors: D
authors: Yuan
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Yun
authors: Y
authors: Zhang
authors: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.|Key Laboratory of Precision Biomedicine, Institute of Zhongyuan Biomedical Sciences, Liaocheng People's hospital, Liaocheng, 252000, Shandong, P. R. China.|The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, P. R. China.
authors: Xun
authors: X
authors: Qu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054422:Chemokine CCL22 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; C515482:CCL22 protein, human; D054422:Chemokine CCL22; D016207:Cytokines; D016328:NF-kappa B; D011134:Polysaccharides; C007789:fucoidan