Metastasis of bone related malignancies ; its mechanisms and experimental treatment

1.肿瘤骨转移的机制及其实验治疗研究探讨了Src酪氨酸激酶、胰岛素样生长因子、核因子-kB和钙粘蛋白-11在肿瘤骨转移中的作用。在实验性骨转移模型中，Src酪氨酸激酶活性升高以及胰岛素样生长因子受体和钙粘蛋白-11的过度表达可增加癌细胞的转移能力。抑制核因子-kB的激活可减少骨转移。2.骨肉瘤肺转移的机制及其实验性治疗通过将小鼠Dunn骨肉瘤细胞注射到小鼠尾静脉异位移植器官的方法来检测骨肉瘤细胞的器官特异性转移。骨肉瘤细胞优先向异位肺组织转移。肺脏培养条件液刺激骨肉瘤细胞生长，牙槽上皮细胞条件液上调骨肉瘤细胞血管内皮生长因子的表达。高转移亚克隆的Dunn骨肉瘤细胞表达VCP，并最终表现出对NF-kB的结构性激活。核因子-kB的抑制剂Parthenolide可以特异性地抑制骨肉瘤细胞的肺转移。

1. Mechanisms of cancer metastasis to bone and its experimental treatmentRole of Src tyrosine kinase, insulin-like growth factor, NF-kB and cadherin-11 in the development of cancer metastasis to bone was investigated. Elevated Src tyrosine kinase activity and overexpression of insulin-like growth factor receptor and cadherin-11 were revealed to increase the metastatic capacity of cancer cells in experimental model of bone metastasis. Inhibition of NF-kB activation reduced bone metastasis. FR167653, a specific inhibitor of p38 MAP kinase, was tested for the ability to inhibit breast cancer metastasis to bone but did not inhibit bone metastasis.,2. Mechanisms of lung metastasis of osteosarcoma and its experimental treatmentOrgan-specific metastasis was tested by injecting mouse Dunn osteosarcoma cells into tail vein of mouse with ectopically implanted organs. Osteosarcoma cells preferentially metastasized to ectopic lung tissue. Conditioned media of lung organ culture stimulated osteosarcoma cell growth and conditioned media of alveolar epithelial cells upregulated VEGF expression of osteosarcoma cells. Highly metastatic subclone of Dunn osteosarcoma cells constitutively expressed VCP and eventually exhibited constitutive activation of NF-kB. Parthenolide, an inhibitor of NF-kB, specifically inhibited lung metastasis of osteosarcoma cells.