Osteosarcoma and chondrosarcoma as targets for virus vectors and herpes simplex virus thymidine kinase/ganciclovir gene therapy.
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.
Ketola
Anna
A
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Määttä
Ann-Marie
AM
Pasanen
Tiina
T
Tulimäki
Kirsi
K
Wahlfors
Jarmo
J
D000256:Adenoviridae / Q000235:genetics; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024201:Bystander Effect / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002813:Chondrosarcoma / Q000235:genetics / Q000628:therapy*; D015774:Ganciclovir / Q000627:therapeutic use* / Q000633:toxicity; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics / Q000627:therapeutic use*; D014161:Transduction, Genetic
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir