title: Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease.
abstract: Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor- overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co-culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1α in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth.
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tsunematsu
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Arakaki
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Otsuka
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kujiraoka
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ushio
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kurosawa
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics / Q000276:immunology*; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma