Protein pathway activation mapping of brain metastasis from lung and breast cancers reveals organ type specific drug target activation.
Protein pathway activation mapping of brain metastasis from lung and breast cancers reveals organ type specific drug target activation.
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肺癌和乳腺癌脑转移的蛋白质通路激活图谱揭示了器官类型特异性药物靶点激活。
DOI：
10.1021/pr200065t
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Wulfkuhle JD
中科院分区：
文献类型：
--
作者：
Improta G;Zupa A;Fillmore H;Deng J;Aieta M;Musto P;Liotta LA;Broaddus W;Petricoin EF 3rd;Wulfkuhle JD
脑转移是系统性癌症最常见的致命并发症，尤其是肺癌（40-50%）和乳腺癌（20-30%）。在这个个性化治疗的时代，迫切需要揭示脑转移的信号结构；然而，对于在大脑微环境中被激活的信号通路知之甚少。利用一项独特的研究，对42例乳腺癌或非小细胞肺癌（NSCLC）患者的脑转移灶进行了研究，利用逆相蛋白微阵列（RPMA）技术，在激光捕获的微解剖肿瘤上皮中测量了128个参与癌症信号传导的关键信号蛋白的磷酸化/激活状态。来自乳腺和肺转移的不同途径激活亚组受到ERBB2、AKT、mTOR、EGFR、SMAD和ERKp38信号的支持。与非小细胞肺癌相比，乳腺癌转移灶中c-ERBB2/IGFR-AKT通路网络的激活显著（p < 0.05）高于非小细胞肺癌转移灶，而非小细胞肺癌脑转移灶中许多EGFR-ERK信号网络成员的相对水平较高。使用RPMA绘制蛋白通路激活图谱揭示了脑转移中信号网络的异质性，这需要预先分层进行靶向治疗，也需要直接分析转移灶。
Brain metastases are the most common fatal complication of systemic cancer, especially of lung (40–50%) and breast (20–30%) cancers. In this era of personalized therapy, there is a critical need to uncover the signaling architecture of brain metastases; however, little is known about what signaling pathways are activated in the context of the brain microenvironment. Using a unique study set of 42 brain metastases from patients with breast or nonsmall cell lung cancer (NSCLC), the phosphorylation/activation states of 128 key signaling proteins involved in cancer signaling were measured in laser capture microdissected tumor epithelium using reverse phase protein microarray (RPMA) technology. Distinct pathway activation subgroups from both breast and lung metastases were underpinned by, among others, ERBB2, AKT, mTOR, EGFR, SMAD, and ERKp38 signaling. Breast cancer metastases showed significantly (p < 0.05) higher activation of the c-ERBB2/IGFR-AKT pathway network compared to NSCLC metastases, whereas NSCLC metastases to the brain exhibited higher relative levels of many members of the EGFR-ERK signaling network. Protein pathway activation mapping using RPMA revealed both the heterogeneity of signaling networks in brain metastases that would require a prior stratification to targeted therapies as well as the requirement of direct analysis of the metastatic lesion.
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拉帕替尼对转移性乳腺癌细胞生长到大脑的影响。
影响因子：
10.3
作者：
Gril, Brunilde;Palmieri, Diane;Bronder, Julie L.;Herring, Jeanne M.;Vega-Valle, Eleazar;Feigenbaum, Lionel;Liewehr, David J.;Steinberg, Seth M.;Merino, Maria J.;Rubin, Stephen D.;Steeg, Patricia S.
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Steeg, Patricia S.
影响因子：
3.3
作者：
Ono, Makiko;Ando, Masashi;Fujiwara, Yasuhiro
通讯作者：
Fujiwara, Yasuhiro
影响因子：
9.7
作者：
Klein, Andreas;Olendrowitz, Christian;Seitz, Susanne
通讯作者：
Seitz, Susanne
影响因子：
254.7
作者：
Landis, SH;Murray, T;Wingo, PA
通讯作者：
Wingo, PA
影响因子：
4.8
作者：
Gondi, Vinai;Mehta, Minesh P.
通讯作者：
Mehta, Minesh P.