title: Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma.
abstract: Nuclear factor-kappa B (NF-κB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-κB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-κB has been developed. To determine whether pulmonary metastasis of osteosarcoma is reduced by inhibiting the action of NF-κB, NF-κB decoy ODN was transfected into the nuclei of murine osteosarcoma cells with high pulmonary metastatic potential, the LM8 cell line, using a three-dimensional alginate spheroid culture model. An in vitro study demonstrated the successful transfection of LM8 cells cultured in alginate beads by 'naked' NF-κB decoy ODN and that the activation of NF-κB signaling was significantly suppressed. Tumor growth was not affected by transfection of NF-κB decoy ODN, however, the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) mRNA was markedly decreased. Furthermore, the transfection of 'naked' NF-κB decoy ODN effectively suppressed pulmonary metastasis in an in vivo alginate bead transplantation model. Our results suggest that NF-κB has a central and specific role in the regulation of tumor metastasis and could be a molecular target for development of anti-metastatic treatments for osteosarcoma.
authors.affiliation: Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Akeda
authors.forename: T
authors.initials: T
authors.lastname: Matsubara
authors.forename: K
authors.initials: K
authors.lastname: Kusuzaki
authors.forename: A
authors.initials: A
authors.lastname: Matsumine
authors.forename: K
authors.initials: K
authors.lastname: Masuda
authors.forename: T
authors.initials: T
authors.lastname: Gemba
authors.forename: A
authors.initials: A
authors.lastname: Uchida
authors.forename: A
authors.initials: A
authors.lastname: Sudo
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009838:Oligodeoxyribonucleotides; D012516:Osteosarcoma / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides