Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells
Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells
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DOI：
10.1016/j.ymthe.2006.05.006
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发表时间：
2006-09-01
影响因子：
12.4
通讯作者：
Castro, Maria G.
中科院分区：
文献类型：
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作者：
Candolfi, Marianela;Curtin, James F.;Castro, Maria G.
多形性胶质母细胞瘤（GBM）是原发性恶性脑肿瘤中最常见的亚型。虽然血清5型腺病毒载体（Ads）已成功用于GBM的临床试验，但Ads感染人胶质瘤细胞的能力和腺病毒受体在GBM细胞中的表达受到挑战。在这份报告中，我们研究了三种分子的表达，这些分子已被证明介导腺病毒进入细胞，即，科萨基和腺病毒受体（CAR）、整合素α（v）β（3）（INT）和I类主要组织相容性复合体（MHCI）在啮齿动物神经胶质瘤细胞系和低传代原代培养物以及来自人GBM的细胞系中的表达。我们将CAR、INT和MHCl的表达水平与几种高容量辅助依赖性腺病毒载体（HC-Ads）引起的转导效率相关联。腺病毒受体的表达水平在所研究的不同GBM细胞中是可变的。HC-Ad介导的治疗性基因表达是有效的，在表达编码的转基因的总靶细胞的20%至80%之间。我们的结果显示CAR、INT或MHCI分子的水平与转基因表达水平或转导的GBM细胞数量之间没有相关性。我们的结论是腺病毒受体的表达水平不能预测其转导效率或生物学功能。
Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alpha(v)beta(3) (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCl with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.