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

血管生成是癌症的关键事件。然而，我们没有任何人体血管生成的体内模型。我们使用人骨移植到NOD/SCID小鼠（Hu-Bone SCID）的皮下组织中来检查人血管生成的体内模型。用抗人CD 31和CD 34抗体通过免疫组织化学染色观察人血管。本研究通过将人乳腺癌（MB-231）和神经母细胞瘤（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，在所有移植的骨和癌组织中观察到人血管生成。用抗血管生成试剂TNP 470（由Takeda Chemical Industries赠送）处理荷瘤Hu-Bone SCID小鼠。因此，TNP 470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。将具有Tek-Fc或neor的克隆接种到Hu-Bone SCID小鼠中。结果，由具有Tek-Fc的克隆形成的肿瘤显著小于由neor克隆形成的肿瘤。通过将人骨移植到NOD/SCID小鼠体内，建立了人血管生成的体内模型。这些模型对于开发新的癌症治疗方法是有用的。

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.