Metastasis of bone related malignancies ; its mechanisms and experimental treatment

骨相关恶性肿瘤的转移；

• 批准号: 13671508
• 负责人: MYOUI Akira
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671508/
• 关键词: bone metastasis; osteosarcoma; tyrosine kinase; MAP kinase; insuline-like growth factor; cadherin; organ-specific metastasis; NF-kB; 骨肉腫; 転移性肺腫瘍; VCP; アポトーシス; パルテノライド; 臓器特異性; 微小環境; 遺伝子発現; 転移性骨腫瘍; 破骨細胞; 肺転移; 増殖因子; 低分子G蛋白; 血管新生因子

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.

1.肿瘤骨转移机制及其实验治疗研究Src酪氨酸激酶、胰岛素样生长因子、NF-κ B和钙粘蛋白-11在肿瘤骨转移中的作用。在骨转移实验模型中，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的过表达被揭示为增加癌细胞的转移能力。抑制NF-κ B活化可减少骨转移。测试了p38 MAP激酶的特异性抑制剂FR 167653抑制乳腺癌骨转移的能力，但不抑制骨转移。2.骨肉瘤肺转移机制及其实验治疗通过将Dunn骨肉瘤细胞注射到异位器官移植小鼠的尾静脉，观察其器官特异性转移。骨肉瘤细胞优先转移到异位肺组织。肺器官培养条件培养基刺激骨肉瘤细胞生长，肺泡上皮细胞条件培养基上调骨肉瘤细胞VEGF表达。Dunn骨肉瘤细胞的高转移性亚克隆组成性表达VCP，并最终表现出NF-κ B的组成性激活。NF-kB抑制剂Parthenidine可特异性抑制骨肉瘤细胞的肺转移。

项目成果

Naka N, et al.: "Expression of SSX genes in human osteosarcomas."Int J Cancer.. 98. 640-642 (2002)

Naka N 等人：“人骨肉瘤中 SSX 基因的表达”。Int J Cancer.. 98. 640-642 (2002)

城山 晋ほか: "転移性骨盤腫瘍の治療成績の検討"中部整災誌. 44. 445-446 (2001)

Susumu Shiroyama 等：“转移性盆腔肿瘤的治疗结果检查”中部灾害管理杂志 44. 445-446 (2001)。

Tatsuya Asai, et al.: "Osteosarcoma after bone marrow transplantation for acute lymphoblastic leukemia."Int J Clin Oncol. 7. 318-321 (2002)

Tatsuya Asai 等人：“急性淋巴细胞白血病骨髓移植后的骨肉瘤。”Int J Clin Oncol。

名井 陽ほか: "整形外科医のための分子生物学「骨肉腫の遺伝子異常」"関節外科. 21. 82-85 (2002)

Yo Nai 等人：“骨科医生的分子生物学：‘骨肉瘤的遗传异常’”关节外科。 21. 82-85 (2002)

Akira Myoui, et al.: "C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis."Cancer Res.. 63. 5028-5033 (2003)

Akira Myoui 等人：“在人类乳腺癌转移的动物模型中，C-SRC 酪氨酸激酶活性与骨和肺中的肿瘤定植相关。”Cancer Res.. 63. 5028-5033 (2003)