Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: a model to elucidate biology and potential targeted therapeutics
Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: a model to elucidate biology and potential targeted therapeutics
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从播散性脑脊液细胞中建立非典型畸胎瘤/横纹肌样瘤（AT/RT）细胞培养物：阐明生物学和潜在靶向治疗的模型
DOI：
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发表时间：
2008
影响因子：
3.9
通讯作者：
D. Strother
中科院分区：
文献类型：
--
作者：
A. Narendran;Lucas Coppes;Aarthi Jayanthan;Michael Coppes;B. Teja;D. Bernoux;David George;D. Strother
非典型的多肌/胸腺肿瘤（AT/RT）是一种高度恶性的中枢神经系统肿瘤，通常会影响婴儿和幼儿。在本报告中，我们描述了能够从AT/RT的婴儿的脑脊液（CSF）获得的肿瘤细胞的持续生长。这些细胞保留了原始肿瘤的形态和生物标志物特征。受体酪氨酸激酶的筛查确定了磷酸化的ERBB4，胰岛素-R，PDGFR和IGF-IR的存在，它们似乎取决于HSP90以维持其活性形式。 IGF-IR活性与来自其他AT/RT细胞系的数据一致。小分子量抑制剂AEW541抑制IGF-IR导致培养的AT/RT细胞的生长抑制。此外，对IGF-II的中和抗体也抑制了这些细胞的生长，这表明该细胞因子具有潜在的自分泌功能。我们还比较了在/RT细胞中培养的细胞系，以识别这些细胞之间的一致药物敏感性模式。除了先前描述的细胞系和异种移植模型外，CSF衍生细胞的连续培养物还可以提供一种研究AT/RT生物学的有效方法，并确定该肿瘤未来治疗剂的潜在靶标。
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm that usually affects infants and young children. In this report, we describe culture conditions that enabled the sustained growth of tumor cells obtained from the cerebrospinal fluid (CSF) of an infant with AT/RT. These cells retained the morphological and biomarker characteristics of the original tumor. A screening of receptor tyrosine kinases identified the presence of phosphorylated ErbB4, Insulin-R, PDGFR and IGF-IR, which appear to depend on Hsp90 to maintain their active form. IGF-IR activity is consistent with data from other established AT/RT cell lines. Inhibition of IGF-IR by the small molecular weight inhibitor AEW541 led to growth suppression of cultured AT/RT cells. In addition, neutralizing antibodies to IGF-II also inhibited the growth of these cells suggesting a potential autocrine function for this cytokine. We also compared cultured AT/RT cells to established cell lines to identify consistent drug sensitivity patterns among these cells. In addition to previously described cell lines and xenograft models, continuous culture of CSF derived cells may also provide an effective way to study the biology of AT/RT and to identify potential targets for future therapeutics for this tumor.
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影响因子：
11.2
作者：
J. Biegel;Jun Zhou;L. Rorke;C. Stenstrom;L. Wainwright;Benjamin Fogelgren
通讯作者：
J. Biegel;Jun Zhou;L. Rorke;C. Stenstrom;L. Wainwright;Benjamin Fogelgren
影响因子：
--
作者：
L. Neckers
通讯作者：
L. Neckers
影响因子：
11.2
作者：
J. Biegel;G. Kalpana;E. Knudsen;R. Packer;C. Roberts;C. Thiele;B. Weissman;Malcolm A. Smith
通讯作者：
J. Biegel;G. Kalpana;E. Knudsen;R. Packer;C. Roberts;C. Thiele;B. Weissman;Malcolm A. Smith
影响因子：
11.2
作者：
Haluska, P;Carboni, JM;Erlichman, C
通讯作者：
Erlichman, C