RRC ID 65752
著者 Kondo T, Tsunematsu T, Yamada A, Arakaki R, Saito M, Otsuka K, Kujiraoka S, Ushio A, Kurosawa M, Kudo Y, Ishimaru N.
タイトル Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease.
ジャーナル Lab Invest
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.
巻・号 96(4)
ページ 468-80
公開日 2016-4-1
DOI 10.1038/labinvest.2015.166
PII labinvest2015166
PMID 26808709
MeSH Animals Autoimmune Diseases / genetics Autoimmune Diseases / immunology Autoimmune Diseases / metabolism Cell Line, Tumor Disease Models, Animal Gene Expression / drug effects Gene Expression / immunology Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / immunology Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Immunohistochemistry Interferon-gamma / genetics Interferon-gamma / immunology Interferon-gamma / metabolism Macrophage Colony-Stimulating Factor / genetics Macrophage Colony-Stimulating Factor / immunology Macrophage Colony-Stimulating Factor / pharmacology Macrophages / classification Macrophages / immunology* Melanoma, Experimental / blood supply Melanoma, Experimental / genetics Melanoma, Experimental / immunology* Mice, Inbred C57BL Mice, Inbred MRL lpr Neovascularization, Pathologic / genetics Neovascularization, Pathologic / immunology* Neovascularization, Pathologic / metabolism Reverse Transcriptase Polymerase Chain Reaction Tumor Burden / genetics Tumor Burden / immunology* Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / immunology Vascular Endothelial Growth Factor A / metabolism
IF 4.197
リソース情報
ヒト・動物細胞 B16F1(RCB2649) B16F10(RCB2630) B16F10/mGM(RCB1158)