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目的 用人骨肉瘤细胞系HOS-98建立人骨肉瘤裸鼠胫骨原位移植模型,以探讨宿主器官微环境对人骨肉瘤细胞侵袭及转移等生物学行为的影响。方法 将人骨肉瘤细胞系HOS-98接种于裸鼠皮下,形成移植瘤,用传代移植瘤组织作为移植材料,进行胫骨原位移植及皮下移植。分别于移植后4周和8周处死小鼠,进行病理形态学检查,并对两种方法在成瘤率、生长方式及侵袭、转移等生物学行为比较。结果 两种移植方式在成瘤率及形态学上无明显不同,胫骨原位移植的潜伏期较短,并且生长快于皮下移植方式。皮下移植瘤呈局限性膨胀生长,有不完整的纤维包膜,瘤内类骨基质较少见,未见肺转移,观察8周时无明显消瘦;而胫骨原位移植瘤侵袭周围组织,可见发生肺转移,8周明显消瘦。原位移植的裸鼠血清ALP水平高于皮下移植者。原位移植的X线检查有明显的类似于人的骨性反应。结论 用人骨肿瘤细胞系HOS-98皮下接种的移植瘤作为移植材料是建立肿瘤异位移植的可行途径,裸鼠胫骨微环境较皮下组织更适合于人骨肉瘤的侵袭及转移表达,裸鼠胫骨原位移植模型的恶性生物学行为更接近临床骨肉瘤患者的体内侵袭及转移实际,该原位移植模型为今后的实验研究提供了更加接近患者实际的实验模型。
Objective To establish an orthotopic tibial transplantation model of human osteosarcoma in human osteosarcoma cell line HOS-98 in order to investigate the effects of host organ microenvironment on the biological behaviors such as invasion and metastasis of human osteosarcoma cells. Methods The human osteosarcoma cell line HOS-98 was inoculated subcutaneously in nude mice to form xenografts. The xenotransplanted xenografts were used as the transplanted materials for tibia orthotopic transplantation and subcutaneous transplantation. The mice were sacrificed at 4 weeks and 8 weeks after transplantation, respectively. Pathological examination was performed. The biological behaviors of the two methods were compared in terms of tumor formation rate, growth pattern, invasion and metastasis. Results There was no significant difference in tumor formation rate and morphology between the two transplantation methods. The tibial orthotopic transplantation had a shorter incubation period and faster growth than the subcutaneous transplantation. Subcutaneous transplanted tumor showed limited expansion and growth, with incomplete fibrous capsule, intratumoral bone matrix less common, no lung metastasis, no significant weight loss observed at 8 weeks; and tibial transplants invade the surrounding tissue, visible Pulmonary metastasis, significant wasting 8 weeks. In situ transplanted nude mice serum ALP levels higher than subcutaneous transplant recipients. X-ray examination of orthotopic transplantation has obvious similar to the human bone reaction. Conclusion The transplanted tumor implanted subcutaneously with human bone tumor cell line HOS-98 as a transplanted material is a viable way to establish heterotopic tumor transplantation. The tibial microenvironment of nude mice is more suitable for invasion and metastasis of human osteosarcoma than that of subcutaneous tissue. The transplanted model of malignant biological behavior is closer to the actual in vivo invasion and metastasis in patients with osteosarcoma. The orthotopic transplantation model provides experimental models that are closer to the actual patient’s experimental study.