title: Proangiogenic TIE2(+)/CD31 (+) macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes.
abstract: Tumor-associated macrophages (TAMs) accumulate in various cancers and promote tumor angiogenesis and metastasis, and thus may be ideal targets for the clinical diagnosis of tumor metastasis with high specificity. However, there are few specific markers to distinguish between TAMs and normal or inflammatory macrophages. Here, we show that TAMs localize in green fluorescent protein-labeled tumors of metastatic lymph nodes (MLNs) from B16F1 melanoma cells but not in necrotic tumor regions, suggesting that TAMs may promote the growth of tumor cells and the progression of tumor metastasis. Furthermore, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures compared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cytokines such as IL-4, IL-10, and TGF-β as well as proangiogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2(+)/CD31(+) macrophages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2(+)/CD31(+) macrophages also heavily infiltrated MLNs from human breast cancer biopsies but not reactive hyperplastic LNs. Thus, TIE2(+)/ CD31(+) macrophages may be a unique histopathological biomarker for detecting metastasis in clinical diagnosis, and a novel and promising target for TAM-specific cancer therapy.
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University Graduate School of Medicine, Incheon, 406-840, Korea.
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Kim
authors.forename: Gun-Hyung
authors.initials: GH
authors.lastname: Kang
authors.forename: Hyungjoon
authors.initials: H
authors.lastname: Noh
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Cha
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Mizuko
authors.initials: M
authors.lastname: Mamura
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Nam
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Kim
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Oh
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis* / Q000276:immunology; D042787:Receptor, TIE-2 / Q000032:analysis* / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042787:Receptor, TIE-2