title: Tumor-associated macrophages promote the metastatic potential of thyroid papillary cancer by releasing CXCL8.
abstract: Tumor-associated macrophages (TAMs) can promote cancer initiation and progression by releasing cytokines. Previously, we have found the density of TAMs correlated with lymph node metastasis in papillary thyroid carcinoma (PTC). However, the mechanisms of how TAMs promote PTC progression remain unclear. In this study, we first showed that the TAMs density in the tumor core was associated with progressive PTC features and TAMs conditioned medium enhanced PTC cells invasion. Cytokine profiling identified a mixed M1/M2 phenotype and CXCL8 was the most consistently abundant cytokine in PTC-derived TAMs. CXCL8 receptors, CXCR1 and CXCR2, were positively stained in PTC cell lines and tissues, though no association with lymph node metastasis or extrathyroid extension. PTC cell invasion was abrogated by anti-CXCL8-neutralizing antibody, whereas addition of exogenous recombinant human CXCL8 enhanced the invasiveness. More importantly, CXCL8 promoted PTC metastasis in vivo. No difference was found for TAMs-derived CXCL8 expression in patients with and without lymph node metastasis or extrathyroid extension. These findings indicated that TAMs may facilitate PTC cell metastasis through CXCL8 and its paracrine interaction with CXCR1/2.
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Fang
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology.
authors.forename: Liyun
authors.initials: L
authors.lastname: Shen
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Pathology and.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Pathology and.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Endocrinology & Metabolism, The Endocrine Institute and the Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shen Yang, Liao Ning 110001, People's Republic of China and.
authors.forename: Haixia
authors.initials: H
authors.lastname: Guan
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai JiaoTong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South Chongqing Road, Shanghai 200025, People's Republic of China gning@sibs.ac.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000818:Animals; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger