RRC ID 33956
Author Kawashima H, Ogose A, Yoshizawa T, Kuwano R, Hotta Y, Hotta T, Hatano H, Kawashima H, Endo N.
Title Expression of the coxsackievirus and adenovirus receptor in musculoskeletal tumors and mesenchymal tissues: efficacy of adenoviral gene therapy for osteosarcoma.
Journal Cancer Sci.
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.
Volume 94(1)
Pages 70-5
Published 2003-1
PMID 12708477
MeSH Adenoviruses, Human / genetics Adenoviruses, Human / metabolism* Alternative Splicing Bone Neoplasms / metabolism* Bone Neoplasms / pathology Bone Neoplasms / therapy Cell Division / genetics Chondrosarcoma / metabolism Chondrosarcoma / pathology Coxsackie and Adenovirus Receptor-Like Membrane Protein Fibrosarcoma / metabolism Fibrosarcoma / pathology Genes, Reporter Genes, p53 Genetic Therapy* Genetic Vectors / genetics Genetic Vectors / metabolism Genetic Vectors / therapeutic use* Green Fluorescent Proteins HeLa Cells / metabolism Histiocytoma, Benign Fibrous / metabolism Histiocytoma, Benign Fibrous / pathology Humans Liposarcoma / metabolism Liposarcoma / pathology Luminescent Proteins / biosynthesis Luminescent Proteins / genetics Mesoderm / metabolism* Neoplasm Proteins / analysis* Neoplasm Proteins / genetics Nerve Sheath Neoplasms / metabolism Nerve Sheath Neoplasms / pathology Neuroectodermal Tumors, Primitive / metabolism Neuroectodermal Tumors, Primitive / pathology Osteosarcoma / metabolism* Osteosarcoma / pathology Osteosarcoma / therapy RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Neoplasm / genetics RNA, Neoplasm / metabolism Receptors, Virus / analysis* Receptors, Virus / genetics Recombinant Fusion Proteins / biosynthesis Recombinant Fusion Proteins / genetics Reverse Transcriptase Polymerase Chain Reaction Rhabdomyosarcoma, Alveolar / metabolism Rhabdomyosarcoma, Alveolar / pathology Sarcoma, Synovial / metabolism Sarcoma, Synovial / pathology Transduction, Genetic Tumor Cells, Cultured / metabolism Tumor Suppressor Protein p53 / physiology
IF 4.751
Times Cited 23
WOS Category ONCOLOGY
Resource
DNA material Ax1 CA gfp (RDB01727)