title: CCL11-induced eosinophils inhibit the formation of blood vessels and cause tumor necrosis.
abstract: We previously demonstrated that IL-18 and CCL11 were highly expressed in an NFSA tumor cell line that showed limited angiogenesis and severe necrosis. However, IL-18 was not responsible for the immune cell accumulation and necrosis. Here, we attempted to clarify the relevance of CCL11 in angiogenesis and tumor formation. We established CCL11-overexpressing MS-K cell clones (MS-K-CCL11) to assess the role of CCL11 in immune cell accumulation and angiogenesis. The MS-K-CCL11 cells did not form tumors in mice. MS-K-CCL11-conditioned medium (CM) and recombinant CCL11 induced macrophage and eosinophil differentiation from bone marrow cells. The MS-K-CCL11-CM effectively recruited the differentiated eosinophils. Furthermore, the eosinophils damaged the MS-K, NFSA and endothelial cells in a dose-dependent manner. Administration of an antagonist of CCR3, a CCL11 receptor, to NFSA tumor-bearing mice restored the blood vessel formation and blocked the eosinophil infiltration into the NFSA tumors. Furthermore, other CCL11-overexpressing LM8 clones were established, and their tumor formation ability was reduced compared to the parental LM8 cells, accompanied by increased eosinophil infiltration, blockade of angiogenesis and necrosis. These results indicate that CCL11 was responsible for the limited angiogenesis and necrosis by inducing and attracting eosinophils in the tumors.
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata, 950-2181, Japan.
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata, 950-2181, Japan.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata, 950-2181, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kurosawa
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata, 950-2181, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata, 950-2181, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Touma
authors.affiliation: Institute for Environmental Sciences, 1-7 Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori, 039-3212, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yanai
authors.affiliation: School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150001, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata, 950-2181, Japan.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054413:Chemokine CCL11 / Q000276:immunology*; D042783:Endothelial Cells / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005354:Fibrosarcoma / Q000098:blood supply / Q000473:pathology*; D006098:Granulocytes / Q000276:immunology*; D051379:Mice; D009281:Naphthalenes; D009389:Neovascularization, Pathologic; D010649:Phenylalanine / Q000031:analogs & derivatives; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors
chemical_list: C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D009281:Naphthalenes; D054397:Receptors, CCR3; C417503:SB 328437; D010649:Phenylalanine