Kim M, Sumerel L A, Belousova N, Lyons G R, Carey D E, Krasnykh V, Douglas J T
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Br J Cancer. 2003 May 6;88(9):1411-6. doi: 10.1038/sj.bjc.6600932.
The coxsackievirus and adenovirus receptor (CAR) is a membrane glycoprotein with a cytoplasmic domain, a transmembrane domain and an extracellular region consisting of two immunoglobulin-like domains, an amino-terminal immunoglobulin variable (IgV)-related domain (D1), which is distal to the cell surface, and a proximal IgC2 domain (D2). The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells. In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect. This finding provides a biological basis for the observation that expression of CAR is downregulated in malignant glioma cells. This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.
柯萨奇病毒和腺病毒受体（CAR）是一种膜糖蛋白，具有一个胞质结构域、一个跨膜结构域和一个由两个免疫球蛋白样结构域组成的细胞外区域，一个氨基末端免疫球蛋白可变（IgV）相关结构域（D1），位于细胞表面远端，以及一个近端IgC2结构域（D2）。柯萨奇病毒和腺病毒受体已被证明在人膀胱和前列腺癌细胞中具有肿瘤抑制活性。在本论文中，我们证明CAR是胶质瘤细胞中的一种肿瘤抑制因子，并且这种抑制作用不需要细胞外D2结构域。这一发现为恶性胶质瘤细胞中CAR表达下调的观察提供了生物学基础。这表明，为了充分发挥腺病毒载体在癌症基因治疗中的潜力，有必要采取策略使腺病毒重新定向以实现不依赖CAR的感染。
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