Trabectedin suppresses osteosarcoma pulmonary metastasis in a mouse tumor xenograft model.
Masahiro InoueKeisuke HoriuchiMichiro SusaEiko TaguchiTakahiro IshizakaHajime RikitakeYusuke MatsuhashiKazuhiro ChibaPublished in: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2021)
Osteosarcoma (OS) is the most common primary bone tumor that mainly affects adolescents and young adults. Although standard treatment modality can achieve up to 60%-70% 5-year survival rate, there has not been any substantial improvement over the past four decades. Furthermore, those presenting with pulmonary metastatic lesions often undergo a highly unfavorable clinical course. Therefore, there is a severely unmet clinical need to provide a more effective treatment for patients with OS. In this study, we show that trabectedin (TBD), a chemotherapeutic agent approved for soft tissue sarcomas, significantly suppresses pulmonary metastasis in a mouse OS xenograft model. In vitro experiments revealed that TBD suppresses cell migration potentially by downregulating the activity of ERK1/2, intracellular molecules that are critically involved in the regulation of cell motility. Collectively, our data may provide a basis for further investigation of TBD on the potential use for OS patients who are at great risk of pulmonary metastasis.
Keyphrases
- pulmonary hypertension
- signaling pathway
- cell migration
- soft tissue
- end stage renal disease
- single cell
- small cell lung cancer
- squamous cell carcinoma
- ejection fraction
- newly diagnosed
- chronic kidney disease
- escherichia coli
- cell proliferation
- electronic health record
- combination therapy
- high grade
- peritoneal dialysis
- case report
- pi k akt
- bone marrow
- risk assessment
- cystic fibrosis
- machine learning
- replacement therapy
- climate change
- bone loss