Overexpression of miR-466 caused a marked downregulation of integrated network of RUNX2 target genes such as osteopontin, osteocalcin, ANGPTs, MMP11 including Fyn, pAkt, FAK and vimentin that are known to be involved in migration, invasion, angiogenesis, EMT and metastasis.
Then, osteolytic bone metastases were largely prevented, because of autophagy failure in metastasis and ossification in bone marrow, with osteocalcin deposition.
Considering that many studies using osteocalcin-driven gene therapy have been conducted to treat hormone refractory metastatic tumors, detailed mechanisms controlling osteocalcin expression needs to be clarified.
This protocol is a phase I/II investigational study of bolus intravenous injections of Ad-OC-E1a for the treatment of chemotherapy-refractory osteogenic sarcoma that has metastasized to the lungs.
The ability of COS31 cells to produce tumors in nude mice (i.e. a small animal model) typical of canine osteosarcoma (i.e. a large animal model) with a similar pathological and biological behavior (e.g. alkaline phosphatase and osteocalcin positive immunostaining, osteoid production, rapid growth, and wide spread metastases) demonstrates the potential utility of COS31 cells as a in vitro and in vivo model system in the development of new strategies in the treatment of human osteosarcoma.