IL-8在循环肿瘤细胞自我种植促进人骨肉瘤进展中的作用机制

摘要

Objective: To explore the mechanism of interleukin-8 ( IL-8 ) in self-seeding of circulating tumor cells promoting the progression of human osteosarcoma. Methods:IL-8 expression of 30 clinical osteosarcoma cases and 10 osteochondroma cases were detected by immunohistochemical SP method;an orthotropic model of human osteo-sarcomawas established by transplanting tumor cells into tibia plateau of nude mice. The treatment group received in-jection ofcirculating tumor cells labeled with RFP from tail vein,and equal volume of PBS for the control group. After secnd,fourth,eightn week,tumor tissues were collected and separate into two parts,one for primary culture,the other for frozen sections to observe the fluorescence of tumor. Immunofluorescent method was employed to observe the IL-8 expression of primary cultured cells. Results:IL-8 was expressed in 93. 3% of osteosarcoma tissues and negative in all osteochondroma tissues. We observed that red fluorescence intensity gradually increased in 3 experimental groups, and the expression level of IL-8 in 3 primary cultured cell groups is gradually increased. The comparison between the experimental groups and control group were all significantly higher than that of control group (P<0. 05),with signifi-cant statistical difference. Conclusion:IL-8 is involved in self-seeding of circulating tumor cells and promotes the progression of human osteosarcoma. This may provide a new strategy for early diagnosis and therapy for osteosarcoma patients.%目的：：探讨IL-8在循环肿瘤细胞自我种植促进人骨肉瘤进展中的作用。方法：免疫组织化学SP法检测30例临床骨肉瘤及10例骨软骨瘤病例肿瘤组织中IL-8表达；建立骨肉瘤原位荷瘤裸鼠模型后,实验组尾静脉注射红色荧光蛋白标记的肿瘤细胞(RFP-F5M2),对照组注射PBS,分别于第2、4、8周后将处理组原位瘤体冰冻切片置于荧光显微镜下观察自我种植细胞荧光强度；对原位肿瘤进行组织块法原代培养,细胞免疫荧光半定量检测IL-8表达水平。结果：93.3%骨肉瘤组织中IL-8表达阳性,骨软骨瘤中IL-8表达均为阴性。冰冻切片显示,随着时间增加,循环肿瘤细胞自我种植现象明显增加,实验组中第2、4、8周原位灶原代培养细胞免疫荧光显示IL-8表达量逐渐增加,并较对照组具有统计学意义(P<0.05)。结论：IL-8在循环肿瘤细胞自我种植促进人骨肉瘤细胞增殖及转移中发挥着重要作用,可为骨肉瘤患者早期诊断和治疗提供一个新的策略。