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

血管生成是癌症的关键事件。然而，我们还没有任何人体血管生成的体内模型。我们研究了将人骨移植到NOD/SCID小鼠皮下组织的体内血管生成模型（Hu-Bone SCID）。用抗人CD31和CD34抗体对人血管进行免疫组化染色。此外，我们将人乳腺癌（MB-231）或神经母细胞瘤（SK-N-DZ）细胞移植到Hu-Bone SCID小鼠体内，建立了人肿瘤血管生成模型。结果，在所有移植骨和癌组织中都观察到人类血管生成。用抗血管生成试剂TNP470（武田化学工业赠送）治疗荷瘤虎骨SCID小鼠。结果表明，TNP470通过抗血管生成作用抑制肿瘤生长。将含有Tek（血管生成素-1受体）-胞外结构域和人免疫球蛋白Fc结构域的表达载体（Tek-Fc）转移到MB-231或SK-N-DZ细胞中。将含有Tek-Fc或neor的克隆接种于Hu-Bone SCID小鼠。结果，具有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，建立了人血管生成的体内模型。这些模型对开发新的癌症疗法很有用。

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.