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S180骨肉瘤细胞TLRs表达及其与肿瘤耐受的相关性[J]. 肿瘤防治研究, 2010, 37(03): 315-318. DOI: 10.3971/j.issn.1000-8578.2010.03.020
引用本文: S180骨肉瘤细胞TLRs表达及其与肿瘤耐受的相关性[J]. 肿瘤防治研究, 2010, 37(03): 315-318. DOI: 10.3971/j.issn.1000-8578.2010.03.020
Expression ofTLRs in S180 Osteosarcoma andRelationship between TLRs and Tumor Tolerance[J]. Cancer Research on Prevention and Treatment, 2010, 37(03): 315-318. DOI: 10.3971/j.issn.1000-8578.2010.03.020
Citation: Expression ofTLRs in S180 Osteosarcoma andRelationship between TLRs and Tumor Tolerance[J]. Cancer Research on Prevention and Treatment, 2010, 37(03): 315-318. DOI: 10.3971/j.issn.1000-8578.2010.03.020

S180骨肉瘤细胞TLRs表达及其与肿瘤耐受的相关性

Expression ofTLRs in S180 Osteosarcoma andRelationship between TLRs and Tumor Tolerance

  • 摘要: 目的 探讨TLRs在诱导S180骨内瘤细胞免疫耐受中的作用,为肿瘤临床的免疫治疗提供新的思路。 方法 建立S180腹水癌早晚期模型,采用RT-PCR方法检测体外S180骨肉瘤细胞和荷瘤鼠体内早晚期S180骨肉瘤细胞TLR1-9 mRNA的表达水平,以及LPS体外刺激S180骨肉瘤细胞前后TGF-β和IL-10 mRNA表达变化,ELISA方法检测LPS体外刺激S180骨肉瘤细胞前后肿瘤上清液中TGF-β蛋白分泌的含量。结果体外S180骨肉瘤细胞表达TLR1-7和TLR9,TLR8不表达。荷瘤鼠体内早晚期S180骨肉瘤细胞TLRs的表达不同,TLR4、9表达早期高于晚期,其中TLR4的高表达有统计学意义(P<0.05);TLR1、2、3、5、6和7表达晚期高于早期,但差异无统计学意义(P>0.05)。10μg/ml 的LPS在不同时间点体外刺激S180骨肉瘤细胞后IL-10 mRNA表达水平均上调,且有时间依赖关系,TGF-β在mRNA和蛋白水平也均有增加。 结论 体外S180骨肉瘤细胞表达多种TLRs,荷瘤鼠体内早晚期S180骨肉瘤细胞TLRs表达的不同在肿瘤发展的不同时期可能发挥不同的作用,S180骨肉瘤细胞TLR4信号通路活化后可能通过促进TGF-β和IL-10的分泌从而参与肿瘤的免疫耐受。

     

    Abstract: Objective To examine theexpression of TLRs in S180 osteosarcoma cells in vitro and at earlierandadvanced stages oftumor-bearing mouse in vivo; To reveal the expression ofTGF-β and IL-10 after stimulating the S180 osteosarcoma cells byLPS in vitro; Andto explorethe mechanisms oftumortolerance inducedby TLRsexpress in tumor cells. Methods S180 ascites carcinoma models were established. The expression of TLRs mRNA in S180 osteosarcoma cells in vitro, and at earlierand advanced stages of tumor-bearing mouse in vivoas well as the changes ofTGF-β and IL-10 after stimulating the S180 osteosarcoma cells byLPS were analyzed by semi-quantitative RT-PCR. The changes of TGF-β protein were detected by ELISA. Results S180 osteosarcoma cellscouldexpress TLR1~7and TLR 9,whilecouldn't express TLR8 in vitro. The expression ofTLR4and TLR9was higher in earlier stage than that in advanced stage. The expression of TLR4wasin significant difference in different stages(P<0.05).Theexpress ofTLR1, TLR2, TLR3,TLR5,TLR6, andTLR7waslower in earlierstagethanthat in advancedstage, whileshowednosignificant difference(P>0.05). Theexpression ofTGF-β andIL-10increasedand depended on time after stimulating S180 osteosarcomacells usingLPS at10μg/mllevel. Conclusion S180 in osteosarcoma cells couldexpress many kinds of TLRs,and the TLRs expression changed in different stage. Thus the express of TLRsin S180 osteosarcoma cellsplayed differentroles indifferent stagesduringthe development oftumor. The activation of TLR4 couldpromote the expression of TGF-β and IL-10,and then enhanced the tolerance of tumor cells.

     

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