Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis.
Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis.
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DOI：
10.1007/s10585-010-9354-8
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发表时间：
2011-01
影响因子：
4
通讯作者：
Noda, Mami
中科院分区：
文献类型：
--
作者：
Seike, Toshihiro;Fujita, Kyota;Yamakawa, Yukiko;Kido, Mizuho A.;Takiguchi, Soichi;Teramoto, Norihiro;Iguchi, Haruo;Noda, Mami
关键词：
脑转移的发生率正在增加，然而，人们对肺癌脑转移的分子机制及其在脑中的发展知之甚少。在本研究中，在脑转移实验模型系统以及肺癌转移的人脑中检查了脑病理学。在实验模型中，在裸鼠心内接种人肺癌衍生 (HARA-B) 细胞 3-6 周后，观察到大范围的脑转移。脑切片显示转移灶周围神经胶质原纤维酸性蛋白（GFAP）阳性星形胶质细胞显着增加。为了阐明星形胶质细胞在肺癌增殖中的作用，在体外分析了原代培养的小鼠星形胶质细胞和HARA-B细胞之间的相互作用。共培养和插入培养证明星形胶质细胞被肿瘤细胞导向因子激活；巨噬细胞迁移抑制因子 (MIF)、白细胞介素 8 (IL-8) 和纤溶酶原激活剂抑制剂 1 (PAI-1)。活化的星形胶质细胞产生白细胞介素6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素1β（IL-1β），进而促进肿瘤细胞增殖。半定量免疫细胞化学显示 HARA-B 细胞上 IL-6 及其亚基 gp130 受体的表达增加。 HARA-B 细胞上也检测到 TNF-α 和 IL-1β 受体，但与星形胶质细胞共培养后下调。星形胶质细胞插入培养还刺激其他肺癌衍生细胞系（PC-9、QG56 和 EBC-1）的增殖。这些结果表明肿瘤细胞和星形胶质细胞相互刺激，这些相互关系对于了解肺癌细胞如何在大脑中转移和发展可能很重要。本文的在线版本 (doi:10.1007/s10585-010-9354-8) 包含补充材料，可供授权用户使用。
The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain. The online version of this article (doi:10.1007/s10585-010-9354-8) contains supplementary material, which is available to authorized users.
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影响因子：
4
作者：
Fitzgerald, Daniel P.;Palmieri, Diane;Hua, Emily;Hargrave, Elizabeth;Herring, Jeanne M.;Qian, Yongzhen;Vega-Valle, Eleazar;Weil, Robert J.;Stark, Andreas M.;Vortmeyer, Alexander O.;Steeg, Patricia S.
通讯作者：
Steeg, Patricia S.
影响因子：
2.9
作者：
Funk, JL;Trout, CR;Reichlin, S
通讯作者：
Reichlin, S
影响因子：
6
作者：
Mihara, Masahiko;Ohsugi, Yoshiyuki;Kishimoto, Tadamitsu
通讯作者：
Kishimoto, Tadamitsu
DOI：
10.1016/0167-5699(90)90106-j
发表时间：
1990-08-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
HERTZ, L;MCFARLIN, DE;WAKSMAN, BH
通讯作者：
WAKSMAN, BH
影响因子：
4.5
作者：
Bauer, Mario;Graebsch, Carolin;Wichmann, Gunnar
通讯作者：
Wichmann, Gunnar