RRC ID 43884
著者 Ihara S, Kida H, Arase H, Tripathi LP, Chen YA, Kimura T, Yoshida M, Kashiwa Y, Hirata H, Fukamizu R, Inoue R, Hasegawa K, Goya S, Takahashi R, Minami T, Tsujino K, Suzuki M, Kohmo S, Inoue K, Nagatomo I, Takeda Y, Kijima T, Mizuguchi K, Tachibana I, Kumanogoh A.
タイトル Inhibitory roles of signal transducer and activator of transcription 3 in antitumor immunity during carcinogen-induced lung tumorigenesis.
ジャーナル Cancer Res
Abstract Stat3 mediates a complex spectrum of cellular responses, including inflammation, cell proliferation, and apoptosis. Although evidence exists in support of a positive role for Stat3 in cancer, its role has remained somewhat controversial because of insufficient study of how its genetic deletion may affect carcinogenesis in various tissues. In this study, we show using epithelium-specific knockout mice (Stat3(Δ/Δ)) that Stat3 blunts rather than supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although Stat3(Δ/Δ) mice did not show any lung defects in terms of proliferation, apoptosis, or angiogenesis, they exhibited reduced urethane-induced tumorigenesis and increased antitumor inflammation and natural killer (NK) cell immunity. Comparative microarray analysis revealed an increase in Stat3(Δ/Δ) tumors in proinflammatory chemokine production and a decrease in MHC class I antigen expression associated with NK cell recognition. Consistent with these findings, human non-small cell lung cancer (NSCLC) cells in which Stat3 was silenced displayed an enhancement of proinflammatory chemokine production, reduced expression of MHC class I antigen, and increased susceptibility to NK cell-mediated cytotoxicity. In addition, supernatants from Stat3-silenced NSCLC cells promoted monocyte migration. Collectively, our findings argue that Stat3 exerts an inhibitory effect on antitumor NK cell immunity in the setting of carcinogen-induced tumorigenesis.
巻・号 72(12)
ページ 2990-9
公開日 2012-6-15
DOI 10.1158/0008-5472.CAN-11-4062
PII 0008-5472.CAN-11-4062
PMID 22659452
MeSH Animals Apoptosis Carcinogens Carcinoma, Non-Small-Cell Lung / chemically induced Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / immunology* Carcinoma, Non-Small-Cell Lung / metabolism Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic* Culture Media, Conditioned Cytokines / biosynthesis HLA Antigens / biosynthesis Humans Killer Cells, Natural / immunology* Lung Neoplasms / chemically induced Lung Neoplasms / immunology* Lung Neoplasms / metabolism Lung Neoplasms / pathology Mice Mice, Knockout RNA Interference RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering STAT3 Transcription Factor / genetics STAT3 Transcription Factor / metabolism* Urethane
IF 9.727
引用数 33
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞