The critical role of an inflammatory cytokine IL-1 in tumor microenvironment on regulation of tumor angiogenesis and metastasis

肿瘤微环境中炎症细胞因子IL-1在调节肿瘤血管生成和转移中的关键作用

• 批准号: 23300350
• 负责人: ONO Mayumi
• 金额: $ 14.14万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23300350/
• 关键词: 炎症; 血管新生; リンパ管新生; IL-1; リンパ節転移; マクロファージ; VEGF-A; VEGF-C; NDRG1; lymphangiogenesis; lymph node metastasis; angiogenesis

Recently it is highlighted that inflammation is closely linked to tumor progression. In this study we demonstrate that IL-1 promotes tumor angiogenesis and lymphangiogenesis through infiltration of tumor supporting macrophages expressing anigogenic and lymphangiogenic factors, resulting in lymph node metastasis of lung cancer cells by comparing highly metastatic human lung cancer cell line expressing higher IL-1alpha with its low metastatic counterpart expressing lower IL-1alpha. Furthermore, we also demonstrate that IL-1/IL-1R-targeted drug significantly suppresses tumor angiogenesis, lymphangiogenesis, and lymph node metastasis. IL-1/IL-1R may thus play crucial roles in malignant progression by lung cancer cells, and the therapeutic efficacy of IL-1R-targeted drugs may lead to an alternative novel strategy to treat lymph node metastasis.

最近，强调炎症与肿瘤进展密切相关。 In this study we demonstrate that IL-1 promotes tumor angiogenesis and lymphangiogenesis through infiltration of tumor supporting macrophages expressing anigogenic and lymphangiogenic factors, resulting in lymph node metastasis of lung cancer cells by comparing highly metastatic human lung cancer cell line expressing higher IL-1alpha with its low metastatic counterpart expressing lower IL-1alpha.此外，我们还证明了IL-1/IL-1R靶向药物可显着抑制肿瘤血管生成，淋巴管生成和淋巴结转移。因此，IL-1/IL-1R可能在肺癌细胞的恶性进展中起关键作用，并且靶向IL-1R的药物的治疗功效可能会导致治疗淋巴结转移的另一种新型策略。

项目成果

The antitumor effect of a novel angiogenesis inhibitor (an octahydronaphthalene derivative) targeting both VEGF receptor and NF-kB pathway

新型血管生成抑制剂（八氢萘衍生物）同时靶向 VEGF 受体和 NF-kB 通路的抗肿瘤作用

• DOI: 10.1002/ijc.26356
• 发表时间: 2012
• 期刊: International Journal of Cancer
• 影响因子: 6.4
• 作者: Watari;K.;Nakamura;M.;Fukunaga;Y.;Furuno;A.;Shibata;T.;Kawahara;A.;Hosoi;F.;Kuwano T.;Kuwano;M.;Ono;M.
• 通讯作者: M.

Y-box binding protein-1 は骨肉腫細胞の増殖を調節し, 骨肉腫の臨床予後と関連する

Y-box结合蛋白1调节骨肉瘤细胞增殖并与骨肉瘤临床预后相关

• 发表时间: 2011
• 作者: 岡田 悠子;小野 眞弓.;他
• 通讯作者: 他

胃癌の腹膜播種における上皮間葉移行(EMT)への NDRG1 の関与

NDRG1参与胃癌腹膜播散的上皮间质转化（EMT）

• 发表时间: 2011
• 作者: 嬉野 浩樹;小野 眞弓.;他
• 通讯作者: 他

オクタヒドロナフタレン誘導体AMF-26はVEGF受容体やNF-kBシグナルを阻害することにより腫瘍の増大を抑制する

八氢萘衍生物 AMF-26 通过抑制 VEGF 受体和 NF-kB 信号抑制肿瘤生长

• 发表时间: 2011
• 作者: 渡公佑;福永裕一;河原明彦;細井文仁;村上雄一;鹿毛政義;小野眞弓
• 通讯作者: 小野眞弓

血管新生・血流正常化を標的としたがん治療.最新がん薬物療法学-がん薬物療法の最新知見-

针对血管生成和血流正常化的癌症治疗 - 癌症药物治疗的最新发现 -

• 发表时间: 2014
• 作者: 渡 公佑;小野 眞弓
• 通讯作者: 小野 眞弓