Research models and mesenchymal/epithelial plasticity of osteosarcoma.

摘要: Most osteosarcomas (OSs) develop from mesenchymal cells at the bone with abnormal growth in young patients. OS has an annual incidence of 3.4 per million people and a 60-70% 5-year surviving rate. About 20% patients have metastasis diagnosis, only 27% metastatic survive longer than 5 years. Mutation tumor suppressors RB1, TP53, REQL4 INK4a and/or deregulation PI3K/mTOR, TGFβ, RANKL/NF-κB IGF pathways been linked to development. However, agents targeting these yielded disappointing clinical outcomes. Surgery chemotherapy remain main treatments OS. Recurrent OSs are commonly resistant therapies. Spontaneous canine models, carcinogen-induced rodent transgenic mouse human patient-derived xenograft cell lines animal developed for studying initiation, progression testing candidate drugs The plasticity regulated by epithelial-to-mesenchymal transition transcription factors (EMT-TFs) such as TWIST1, SNAIL, SLUG, ZEB1 ZEB2 plays important role maintenance status promotion invasion cells. Multiple microRNAs including miR-30/9/23b/29c/194/200, proteins SYT-SSX1/2 fusion OVOL2, other that inhibit AMF/PGI LRP5 can suppress either expression or activity EMT-TFs increase epithelial features metastasis. Further understanding molecular mechanisms regulate should provide potential targets therapeutic strategies improving treatment.