Anti-EGFR-mediated radiosensitization as a result of augmented EGFR expression
Anti-EGFR-mediated radiosensitization as a result of augmented EGFR expression
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DOI：
10.1016/j.ijrobp.2004.01.053
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发表时间：
2004-01-01
影响因子：
7
通讯作者：
Raisch, KP
中科院分区：
文献类型：
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作者：
Bonner, JA;Buchsbaum, DJ;Raisch, KP
目的：表皮生长因子受体（EGFR）表达升高与几种恶性肿瘤标准治疗后的不良预后相关。然而，目前尚不清楚EGFR表达的绝对水平是否影响抗EGFR治疗的放射增敏特性。更好地理解这个问题将有助于设计提供这些治疗的方案。为了探讨这个问题，细胞（LS 174 T），不显示固有的抗EGFR治疗诱导的放射增敏被选择的研究，可能会增强EGFR expression.Materials和方法：人结肠癌细胞（LS 174 T），这并没有表现出放射增敏抗EGFR治疗，被用于这些研究。(Also这些细胞对抗EGFR治疗的抗增殖作用没有反应。使用标准转染技术（真核表达载体）以及腺病毒构建体来增强EGFR表达，以导致EGFR表达增强的方式转导LS 174 T细胞。随后，进行标准增殖研究以测试抗EGFR处理（抗EGFR单克隆抗体：IMC-C225）的放射增敏特性。稳定的转染子LS174T.EGFR细胞对抗EGFR处理的抗增殖作用有响应，与亲本LS 174 T细胞相反。当细胞被AdEGFR感染时，也证明了类似的结果。此外，LS174T.EGFR细胞对抗EGFR治疗的放射增敏特性有反应（IMC-C225），而亲本细胞则没有。尽管EGFR表达水平在许多肿瘤模型中具有预后意义，但细胞对单独的抗EGFR治疗或该治疗与放射或化学治疗的组合的反应，这取决于许多因素，这些因素不一定与肿瘤细胞的固有EGFR表达相关。然而，本文报道的研究表明，当LS 174 T细胞被转导以显示增加的EGFR表达时，它们变得对抗EGFR治疗的放射增敏特性有响应。(C)2004年爱思唯尔公司
Purpose: Elevated epidermal growth factor receptor (EGFR) expression has correlated with a poor prognosis after standard treatment of several malignancies. However, it is not clear whether the absolute level of EGFR expression affects the radiosensitizing properties of anti-EGFR treatments. A better understanding of this question would be helpful for the design of protocols that deliver these treatments. To explore this question, cells (LS174T) that did not display inherent anti-EGFR treatment-induced radiosensitization were selected for studies that could potentially enhance EGFR expression.Materials and Methods: Human colon carcinoma cells (LS174T), which did not show radiosensitization by anti-EGFR treatments, were employed for these studies. (Also, these cells were not responsive to the antiproliferative effects of anti-EGFR treatment.) Using standard transfection techniques (eukaryotic expression vector) as well as an adenoviral construct to enhance EGFR expression., LS174T cells were transduced in a manner that resulted in enhanced expression of EGFR. Subsequently, standard proliferation studies were performed to test the radiosensitizing properties of anti-EGFR treatment (an anti-EGFR monoclonal antibody: IMC-C225).Results: Studies were undertaken to stably transfect LS174T cells with EGFR. The stable transfectants, LS174T.EGFR cells, were responsive to the antiproliferative effects of anti-EGFR treatment, in contrast to the parent LS174T cells. Similar results were demonstrated when the cells were infected with AdEGFR. Additionally, the LS174T.EGFR cells were responsive to the radiosensitizing properties of anti-EGFR treatment (IMC-C225), whereas the parent cells were not.Conclusions: Although the level of EGFR expression is of prognostic significance in many tumor models, the response of cells to anti-EGFR treatment alone, or combinations of this treatment with radiation or chemotherapy, depends upon many factors that are not necessarily related to the inherent EGFR expression of the tumor cells. However, the studies reported herein, demonstrate that when LS174T cells were transduced to show increased EGFR expression, they became responsive to the radiosensitizing properties of anti-EGFR treatments. (C) 2004 Elsevier Inc.