ADAM-12 as a diagnostic marker for the proliferation, migration and invasion in patients with small cell lung cancer.
ADAM-12 as a diagnostic marker for the proliferation, migration and invasion in patients with small cell lung cancer.
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DOI：
10.1371/journal.pone.0085936
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Pan F
中科院分区：
文献类型：
--
作者：
Shao S;Li Z;Gao W;Yu G;Liu D;Pan F
小细胞肺癌（SCLC）是一种高度侵袭性的肿瘤，以恶性转移为特征。大约90%的患者死于广泛转移。细胞外基质（extracellular matrix，ECM）是阻止细胞侵袭和转移的天然屏障。因此，为了发生广泛的转移，必须发生ECM的降解。去整合素和金属蛋白酶（ADAM）是一种多结构域蛋白酶，其在肿瘤发生以及肿瘤发展、侵袭和转移中起重要作用。然而，关于亚当斯在小细胞肺癌中的表达和作用的报道很少。本研究探讨亚当斯在SCLC增殖、侵袭和转移中的表达及其作用。共150例SCLC组织样本通过免疫组化检测亚当斯表达。ADAM-12在72.67%的样本中大量表达，其他亚当斯在10%-40%的样本中表达。采用酶联免疫吸附法（ELISA）检测70例小细胞肺癌患者和40例正常人血清和尿液中ADAM-12的水平。ADAM-12在SCLC患者中的表达显著高于健康对照组，并且在广泛疾病患者中的表达显著高于局限性疾病患者。通过使用特异性siRNA沉默H1688细胞中ADAM-12的表达显著降低细胞增殖、侵袭和转移。补充ADAM-12-L或-S的表达可显著增强H345细胞的增殖、侵袭和转移能力。具有转移性SCLC的动物模型也表现出随着侵袭和转移的增强而沿着增加的ADAM-12表达。总之，ADAM-12是一个独立的预后因子和诊断标志物，参与了小细胞肺癌的增殖、侵袭和转移。
Small cell lung cancer (SCLC) is highly aggressive and is characterized by malignant metastasis. Approximately 90% of patients die due to extensive metastasis. The extracellular matrix (ECM) is a natural barrier that can prevent cellular invasion and metastasis. Therefore, degradation of the ECM must take place in order for extensive metastasis to occur. A disintegrin and metalloprotease (ADAM) is a multi-domain protease that plays an important role in tumorigenesis, as well as tumor development, invasion and metastasis. However, there have been few reports on the expression and role of ADAMs in SCLC. In the current study, the expression and role of ADAMs in SCLC proliferation, invasion and metastasis was investigated. A total of 150 SCLC tissue samples were examined by immunohistochemistry for ADAMs expression. ADAM-12 was found to be abundantly expressed in 72.67% samples and other ADAMs were found to be expressed in 10% to 40% of samples. ADAM-12 levels in serum and urine, from 70 SCLC patients and 40 normal controls, were also measured using ELISA. ADAM-12 expression was significantly higher in SCLC patients than in healthy controls and in patients with extensive disease compared to those with more limited disease. Silencing the expression of ADAM-12 in H1688 cells through the use of specific siRNA significantly reduced cellular proliferation, invasion and metastasis. Supplementing the expression of ADAM-12-L or -S in H345 cells, significantly enhanced cellular proliferation, invasion and metastasis. Animal models with metastatic SCLC also exhibited increased expression of ADAM-12 along with enhanced invasion and metastasis. In brief, ADAM-12 is an independent prognostic factor and diagnostic marker, and is involved in the proliferation, invasion and metastasis of SCLC.
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DOI：
10.1083/jcb.200612046
发表时间：
2007-07-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Atfi A;Dumont E;Colland F;Bonnier D;L'helgoualc'h A;Prunier C;Ferrand N;Clément B;Wewer UM;Théret N
通讯作者：
Théret N
影响因子：
45.3
作者：
Michael, M;Babic, B;Shepherd, FA
通讯作者：
Shepherd, FA
影响因子：
8
作者：
Liu, YJ;Xu, Y;Yu, Q
通讯作者：
Yu, Q
影响因子：
6.4
作者：
O'Shea, C;McKie, N;Duffy, MJ
通讯作者：
Duffy, MJ
影响因子：
13.5
作者：
Le Pabic, H;Bonnier, D;Théret, N
通讯作者：
Théret, N