Model for human cancer invasion/metastasis using NOD/SCID mice

使用 NOD/SCID 小鼠建立人类癌症侵袭/转移模型

• 批准号: 11670193
• 负责人: YAMADA Taketo
• 金额: $ 2.3万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670193/
• 关键词: human cancer; invasion; NOD; SCID mice; angiogenesis; angiopoietin; tek tyrosine kinase; metastasis; 癌; レトロウィルスベクター; レトロウイルスベクター

Angiogenesis is a crucial event for cancer. However we don't have any in vivo models for human angiogenesis. We examined in vivo model for human angiogenesis using transplantation of human bone into subcutaneous tissue of NOD/SCID mice(Hu-Bone SCID). Human vessels were observed by immunohistochemical stainings with anti-human CD31 and CD34 antibodies. Futhermore we developed human tumor angiogenesis model by transplantation of human breast carcinoma(MB-231) or neuroblastoma(SK-N-DZ) cells into Hu-Bone SCID mice. As a result, human angiogenesis was observed in all transplanted bones and cancer tissues. The tumor-bearing Hu-Bone SCID mice were treated with an anti-angiogenetic reagent, TNP470(gifted by Takeda Chemical Industries). As a result, TNP470 inhibited the tumor growth via the anti-angiogenetic effect. An expression vector(Tek-Fc) containing Tek(a receptor for angiopoitin-1)-extracellular domain and human immunoglobulin Fc domain was transfered into MB-231 or SK-N-DZ cells. Clones with Tek-Fc or neor were inoculated into Hu-Bone SCID mice. As a result, tumors formed by the clones with Tek-Fc were significantly smaller than tumors formed by the neor clones. The in vivo models for human angiogenesis were established using the transplantation of human bone into NOD/SCID mice. These models are useful for the development for new cancer theraptes.

血管生成是癌症的关键事件。然而，我们还没有任何关于人类血管生成的体内模型。我们研究了人骨移植到NOD/SCID小鼠皮下组织(人骨SCID)的体内血管生成模型。用抗人CD31和CD34抗体进行免疫组织化学染色，观察血管的形态。此外，我们还将人乳腺癌(MB-231)和神经母细胞瘤(SK-N-DZ)细胞移植到人SCID小鼠体内，建立了人肿瘤血管生成模型。结果，在所有移植的骨骼和癌症组织中都观察到了人类血管生成。荷瘤的人骨SCID小鼠用一种抗血管生成的试剂TNP470(武田化学工业公司提供)进行治疗。因此，TNP470通过抗血管生成作用抑制肿瘤生长。将含有血管生成素-1受体Tek胞外区和人免疫球蛋白Fc区的表达载体(Tek-Fc)转入MB-231或SK-N-DZ细胞。将带有Tek-Fc或NeOR的克隆接种到人SCID小鼠体内。结果表明，携带Tek-FC的克隆形成的肿瘤明显小于新克隆形成的肿瘤。将人骨移植到NOD/SCID小鼠体内，建立人血管生成的体内模型。这些模型对新的癌症治疗方法的开发是有用的。

项目成果

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Yamaoka T: "Diabetes and pancreatic tumours in transgenic mice expressing Pax 6."Diabetologia. 43. 332-339 (2000)

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Yamaoka T, Yoshino K, Yamada T, Idehara C, Hoque MO, Moritani M, Yoshimoto K, Hata J, Itakura M: "Diabetes and tumor formation in transgenic mice expressing reg I."Biochem Biophys Res Commun. 278(2). 368-76 (2000)

Yamaoka T、Yoshino K、Yamada T、Idehara C、Hoque MO、Moritani M、Yoshimoto K、Hata J、Itakura M：“表达 reg I 的转基因小鼠中的糖尿病和肿瘤形成。”Biochem Biophys Res Commun。

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