Abstract
Recombinant adenovirus is used as a competent vector in a wide spectrum of cancer gene therapies. Adenovirus infection depends on coxsackievirus and adenovirus receptor (CAR)-mediated virus attachment to the cell surface. However, the expression levels of CAR and the efficiency of adenoviral gene transduction in musculoskeletal tumors have not been systematically investigated. To study the feasibility of gene therapy in musculoskeletal tumors, the expression levels of CAR and the antiproliferative effect of an adenovirally transduced wild-type p53 tumor suppressor gene were examined in 15 distinct musculoskeletal tumor cell lines, 19 tumor tissue samples, and the corresponding pathologically unremarkable mesenchymal tissues. The expression levels of the CAR gene were significantly higher in six of seven osteosarcoma cell lines and two of five osteosarcoma tissue samples than in the other cell lines, musculoskeletal tumors, and mesenchymal tissues. CAR expression levels were closely correlated with adenoviral gene transduction efficiency and the antiproliferative effect of a transduced adenoviral p53 gene in the tested cell lines. In addition, an immunocytochemical study confirmed that transfected green fluorescent protein (GFP) borne by Ad-CAG-GFP was expressed at the cell surface of CAR-positive cells. These results indicate that CAR expression is a critical determinant of transduction efficiency in adenovirus-based gene therapy. Most osteosarcomas appeared to express high levels of CAR, and thus adenovirus-mediated p53 gene therapy is likely to be suitable for the treatment of such tumors.
MeSH terms
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Adenoviruses, Human / genetics
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Adenoviruses, Human / metabolism*
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Alternative Splicing
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Bone Neoplasms / metabolism*
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Bone Neoplasms / pathology
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Bone Neoplasms / therapy
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Cell Division / genetics
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Chondrosarcoma / metabolism
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Chondrosarcoma / pathology
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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Fibrosarcoma / metabolism
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Fibrosarcoma / pathology
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Genes, Reporter
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Genes, p53
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Genetic Therapy*
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Genetic Vectors / genetics
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Genetic Vectors / metabolism
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Genetic Vectors / therapeutic use*
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Green Fluorescent Proteins
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HeLa Cells / metabolism
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Histiocytoma, Benign Fibrous / metabolism
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Histiocytoma, Benign Fibrous / pathology
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Humans
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Liposarcoma / metabolism
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Liposarcoma / pathology
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Luminescent Proteins / biosynthesis
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Luminescent Proteins / genetics
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Mesoderm / metabolism*
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Neoplasm Proteins / analysis*
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Neoplasm Proteins / genetics
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Nerve Sheath Neoplasms / metabolism
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Nerve Sheath Neoplasms / pathology
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Neuroectodermal Tumors, Primitive / metabolism
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Neuroectodermal Tumors, Primitive / pathology
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Osteosarcoma / metabolism*
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Osteosarcoma / pathology
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Osteosarcoma / therapy
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Neoplasm / genetics
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RNA, Neoplasm / metabolism
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Receptors, Virus / analysis*
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Receptors, Virus / genetics
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Rhabdomyosarcoma, Alveolar / metabolism
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Rhabdomyosarcoma, Alveolar / pathology
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Sarcoma, Synovial / metabolism
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Sarcoma, Synovial / pathology
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Transduction, Genetic
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Tumor Cells, Cultured / metabolism
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Tumor Suppressor Protein p53 / physiology
Substances
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CLMP protein, human
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Coxsackie and Adenovirus Receptor-Like Membrane Protein
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Luminescent Proteins
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Virus
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Recombinant Fusion Proteins
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Tumor Suppressor Protein p53
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Green Fluorescent Proteins