ADAM17 promotes glioma cell malignant phenotype.
ADAM17 promotes glioma cell malignant phenotype.
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DOI：
10.1002/mc.20772
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发表时间：
2012-02
影响因子：
4.6
通讯作者：
Chopp, Michael
中科院分区：
文献类型：
--
作者：
Zheng, Xuguang;Jiang, Feng;Katakowski, Mark;Lu, Yong;Chopp, Michael
去整合素和金属蛋白酶-17(ADAM17)参与了几种膜结合生长因子和细胞因子的蛋白水解性胞外结构域脱落。在某些病理条件下，如中风和癌症，ADAM17的表达和活性增加。ADAM17促进神经前体细胞迁移，并有助于中风后的神经再生和乳腺癌的生长和侵袭。在本研究中，我们试图阐明ADAM17是否与胶质瘤的进展有关。为此，我们研究了ADAM17在U87人脑胶质瘤细胞体外增殖、侵袭和管状形成以及体内肿瘤生长中的作用。分别用人ADAM17高表达的质粒和ADAM17的siRNA稳定地转染U87细胞，以建立ADAM17在胶质瘤细胞中的高表达或低表达。ADAM17抑制剂TAPI-2和PI3K-AKT抑制剂LY294002分别阻断ADAM17的高表达和激活的PI3K-AKT通路。用四甲基偶氮唑蓝(四甲基偶氮唑蓝)比色法、溴脱氧尿嘧啶核苷掺入法、生长曲线法和磺胺若丹明B比色法检测细胞增殖。采用Matrigel侵袭实验检测U87细胞穿透细胞外基质的能力。进行Matrigel管形成实验以测试毛细管形成能力。Western印迹法检测不同ADAM17表达水平下U87细胞EGFR-PI3K-Akt通路的激活情况。我们的数据表明，ADAM17通过增加增殖、侵袭、血管生成和体内肿瘤生长来促进U87恶性表型。ADAM17抑制剂和A17-shRNA体内转染组裸鼠移植瘤生长明显受到抑制。ADAM17siRNA、TAPI2和LY294002可抑制ADAM17siRNA、TAPI2和LY294002对U87细胞转化生长因子α、血管内皮生长因子分泌和血管内皮生长因子表达的影响。ADAM17激活，而ADAM17 siRNA、TAPI-2和LY294002失活EGFR-PI3K-AKT信号通路，与U87细胞恶性表型变化相关。本研究提示ADAM17通过激活EGFR-PI3K-AKT信号通路参与脑胶质瘤的进展。
A disintegrin and metalloproteinase-17 (ADAM17) is involved in proteolytic ectodomain shedding of several membrane-bound growth factors and cytokines. The expression and activity of ADAM17 increase under some pathological conditions such as stroke and cancer. ADAM17 promotes neural progenitor cell migration and contributes to neurogenesis after stroke and breast cancer growth and invasion. In the present study, we sought to elucidate whether ADAM17 contributes to glioma progression. To this end, we examined the role of ADAM17 in the proliferation, invasion, and tube formation of U87 human glioma cells in vitro and tumor growth in vivo. Stable transfection of the U87 cell line with either a plasmid for over-expression of human ADAM17, or a siRNA to ADAM17 was employed in this study to establish high or low ADAM17 expression in glioma cells, respectively. For study of mechanism, the ADAM17 inhibitor TAPI-2 and the PI3K-AKT inhibitor LY294002 were used to counteract high ADAM17 expression and the activated PI3K-AKT pathway, respectively. Proliferation of glioma cells were tested by thiazolyl blue tetrazolium bromide (MTT) assay, Bromodeoxyuridine incorporation assay, growth curve, and sulforhodamine B assay. Matrigel invasion assays were used to assess the ability of U87 cells to penetrate the extra-cellular matrix (ECM). A Matrigel tube formation assay was performed to test capillary tube formation ability. EGFR-PI3K-Akt pathway activation in U87 cells under different ADAM17 expression levels were tested by Western blot. Our data show that ADAM17 promotes the U87 malignant phenotype by increased proliferation, invasion, angiogenesis and in vivo tumor growth. Tumor growth in nude mice was significantly inhibited by ADAM17 inhibitor and A17-shRNA in vivo transfection. TGF-α, VEGF secretion and VEGF expression was increased by ADAM17 and counteracted by ADAM17 siRNA, TAPI-2, and LY294002 in U87 cells. ADAM17 activated, whereas ADAM17 siRNA, TAPI-2, and LY294002 deactivated the EGFR-PI3K-AKT signal pathway, which correlated with U87 cell malignant phenotype changes. This study suggests ADAM17 contributes to glioma progression through activation of the EGFR-PI3K-AKT signal pathway.
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影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
影响因子：
11.4
作者：
Borrell-Pagès, M;Rojo, F;Arribas, J
通讯作者：
Arribas, J
肿瘤发生和血管生成中的 PI3K/PTEN 信号传导。
DOI：
10.1016/j.bbapap.2007.09.008
发表时间：
2008-01-01
影响因子：
3.2
作者：
Jiang, Bing-Hua;Liu, Ling-Zhi
通讯作者：
Liu, Ling-Zhi
影响因子：
6.2
作者：
COLLINS, VP
通讯作者：
COLLINS, VP
影响因子：
6.3
作者：
Katakowski, Mark;Chen, Jieli;Chopp, Michael
通讯作者：
Chopp, Michael