Ketola Anna, Määttä Ann-Marie, Pasanen Tiina, Tulimäki Kirsi, Wahlfors Jarmo
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Int J Mol Med. 2004 May;13(5):705-10.
Osteosarcoma and chondrosarcoma, the most prevalent primary malignant tumors of the bone, have been demonstrated to be potential target diseases for herpes simplex virus type 1 thymidine kinase (HSV-TK)/ganciclovir (GCV) suicide gene therapy. However, the utility of this gene therapy form for bone tumor cells has not been studied systematically. In this report we show, with the aid of three osteosarcoma cell lines (Saos-2, U-2-OS and MG-63) and one chondrosarcoma cell line (SW1353) that: i) these tumor cells were permissive for adenovirus- or lentivirus-mediated gene delivery; ii) the cell lines appeared to be good or excellent targets for HSV-TK/GCV gene therapy; and iii) the extent of HSV-TK/GCV cytotoxic effect correlated with the presence of the 'bystander effect' in these cells. Our results also suggest that lentiviruses are potential vectors for bone cancer gene therapy. They transduced all four cell lines with high efficiency and provided HSV-TK expression level that was sufficient for cytotoxicity and bystander effect comparable to that obtained with adenovirus vectors.
骨肉瘤和软骨肉瘤是最常见的原发性骨恶性肿瘤，已被证明是单纯疱疹病毒1型胸苷激酶（HSV-TK）/更昔洛韦（GCV）自杀基因治疗的潜在目标疾病。然而，这种基因治疗形式对骨肿瘤细胞的效用尚未得到系统研究。在本报告中，我们借助三种骨肉瘤细胞系（Saos-2、U-2-OS和MG-63）和一种软骨肉瘤细胞系（SW1353）表明：i）这些肿瘤细胞允许腺病毒或慢病毒介导的基因传递；ii）这些细胞系似乎是HSV-TK/GCV基因治疗的良好或极佳靶点；iii）HSV-TK/GCV细胞毒性作用的程度与这些细胞中“旁观者效应”的存在相关。我们的结果还表明，慢病毒是骨癌基因治疗的潜在载体。它们高效转导了所有四种细胞系，并提供了足以产生细胞毒性和旁观者效应的HSV-TK表达水平，与腺病毒载体获得的水平相当。
