完整瘤组织块原位移植法建立人成骨肉瘤转移模型

Nude mouse metastatic models of human osteosarcoma constructed using orthotopic implantation of histologically intact tissue

目的：建立人成骨肉瘤裸鼠转移模型。方法：采用完整瘤组织块原位移植法获得裸鼠自发性肺转移模型，并对转移模型进行影像学检查、组织学检查及 PCR同源性分析。 结果： 建立裸鼠体内人成骨肉瘤转移模型，其自发性肺转移率达到 100％，肝转移率达 30％。影像学检查及组织学检查均与人成骨肉瘤临床情况相似， PCR同源性分析证实裸鼠肺部转移灶为人成骨肉瘤细胞。结论：裸鼠体内人成骨肉瘤自发性转移模型模拟了临床发病过程，对人成骨肉瘤的治疗、局部肿瘤的生长及转移机制的研究提供了更为理想的模型。

Objective: To establish a new human osteosarcoma spontaneous metastasis model using orthotopic transplantation of histologically intact tumor tissue. Methods: We have utilized orthotopic transplantation of histologically intact tumor tissue into the tibia of nude mice. Intact tumor pieces were obtained from the nude mice of subcutaneously growing human osteosarcoma xenografts. Animals were sacrificed and autopsied 6 weeks after transplantation and examined macroscopically and microscopically for local tumor growth and metastases. Radiographic examination and human Alu sequence PCR amplification were applied to characterize the metastasis model. Results: All mice developed local intratibial bone tumors were radiographically and histologically similar to primary human osteosarcoma. Lung metastases were observed in 20(100％ ) mice.Liver metastases were observed in 6(30％ ) mice. The microscopic appearance of the metastases was similar to that observed in the donor patient s tumor, corresponding subcutaneous xenografts and orthotopically transplanted intratibial tumors. The result of human Alu sequence PCR amplification showed that the metastatic tumor were composed of human osteosarcoma cells. Conclusion: This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situation and could thus be useful for studies on local tumor growth,metastasis formation and therapy.