Characterization of a rat model with site-specific bone metastasis induced by MDA-MB-231 breast cancer cells and its application to the effects of an antibody against bone sialoprotein
Characterization of a rat model with site-specific bone metastasis induced by MDA-MB-231 breast cancer cells and its application to the effects of an antibody against bone sialoprotein
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DOI：
10.1002/ijc.20840
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发表时间：
2005-06-10
影响因子：
6.4
通讯作者：
Berger, MR
中科院分区：
文献类型：
--
作者：
Bäuerle, T;Adwan, H;Berger, MR
骨转移是某些肿瘤性疾病如乳腺癌、前列腺癌和肺癌的严重并发症，但对这种向骨性的原因知之甚少。我们的目的是建立一个生理相关的动物模型，其特点是溶骨性病变局限于后腿的裸大鼠。为此，我们将1 × 10（5）个转染GFP的MDA-MB-231人乳腺癌细胞注射到腹壁浅动脉中，该动脉是股动脉和髂动脉之间的闭塞血管。通过X线、计算机断层扫描和骨化学评估，溶骨性病变仅发生在动物的股骨、胫骨和腓骨中。在一系列96只大鼠中，肿瘤发生率为93%，并且在肿瘤细胞接种后110天观察到病变大小增加。当将该动物模型应用于抗骨唾液蛋白（BSP）抗体的作用时，在动脉内肿瘤细胞注射之前预孵育细胞（2小时，600 μ g/ml抗BSP）后观察到溶骨性病变尺寸显着减小，导致肿瘤植入后第60天的T/C%为19（p < 0.05）。此外，溶骨性病变的大小也显着减少后，s.c.用抗体处理动物（在肿瘤植入后5天内20 mg/kg抗BSPx 3），导致在肿瘤细胞植入后第60天30 T/C%（p < 0.05）。总之，新的位点特异性溶骨性病变的大鼠模型提供了体内证据，即MDA-MB-231（GFP）细胞的预孵育和肿瘤植入后用抗BSP抗体治疗大鼠可显著降低骨溶解性病变的大小。(c)2005 Wiley-Liss，Inc.
Metastasis into the skeleton is a serious complication of certain neoplastic diseases such as breast, prostate and lung cancer, but the reasons for this osteotropism are poorly understood. Our aim was to establish a physiologically relevant animal model that is characterized by osteolytic lesions confined to the hind leg of nude rats. For this purpose, we injected 1 x 10(5) MDA-MB-231 human breast cancer cells transfected with GFP into the superficial epigastric artery, which is an anastomosing vessel between the femoral and iliac arteries. As assessed with the aid of X-rays, computed tomography and immunohistochemisty, osteolytic lesions occurred exclusively in the femur, tibia and fibula of the animals. The tumor take rate was 93% in a series of 96 rats and the increase in lesion size was observed up to 110 days after tumor cell inoculation. When applying this animal model to the effects of an antibody against bone sialoprotein (BSP), a significantly reduced osteolytic lesion size was observed after preincubation of cells (2 hr, 600 mu g/ml anti-BSP) prior to intra-arterial tumor cell injection resulting in 19 T/C% at day 60 after tumor implantation (p < 0.05). In addition, the osteolytic lesion size was also significantly reduced after s.c. treatment of the animals with the antibody (20 mg/kg anti-BSPx3 within 5 days after tumor implantation), resulting in 30 T/C% at day 60 after tumor cell implantation (p < 0.05). In conclusion, the novel rat model for site-specific osteolytic lesionspprovides in vivo evidence that preincubation of MDA-MB-231(GFP) cells and treatment of rats after tumor implantation with an antibody against BSP significantly reduces the size of lytic lesions in bone. (c) 2005 Wiley-Liss, Inc.