白细胞介素-1α诱导间充质干细胞产生免疫抑制作用促进前列腺癌细胞生长的研究

Interleukin-1α induces immunosuppression by mesenchymal stem cells in promoting the growth of prostate cancer cells

目的 探索间充质干细胞（MSCs）在小鼠体内肿瘤生长微环境中促进前列腺癌生长的机制. 方法 2013年4-10月,将以炎症因子白细胞介素-1α（IL-1α）预处理的MSCs或其细胞培养上清以及未经IL-1α预处理的MSCs或其细胞培养上清与C57BL/6来源的前列腺癌细胞RM-1共同移植到C57BL/6和BALB/c的小鼠腋窝皮下,建立同源及异源的小鼠前列腺癌皮下移植瘤模型,以未经处理的RM-1细胞作为对照组,检测前列腺癌的生长情况.同时在体外实验中检测MSCs对脾细胞增殖的影响. 结果 经MSCs、MSCs培养上清、IL-1α处理的MSCs及培养上清处理的RM-1细胞C57BL/6小鼠皮下移植瘤重量分别为（3.4±0.2）、（3.3±0.2）、（4.9±0.5）、（5.2±0.6）g,与对照组（2.4±0.2）g比较差异均有统计学意义（P＜0.05）.以上4组细胞在BALB/c小鼠均有一定的成瘤率,接种30 d时分别为50％、50％、80％、80％,对照组为0.IL-1α预处理组的脾细胞数量低于对照组及未处理组,差异均有统计学意义（P＜0.05）. 结论 IL-1α预处理的MSCs可以促进前列腺癌细胞在小鼠体内的生长,原因可能是由于炎症因子诱导MSCs产生免疫抑制,进而导致肿瘤细胞发生免疫逃逸.

Objective To explore the preliminary mechanism of mesenchymal stem cells （MSCs） in promoting prostate cancer proliferation in tumor inflammatory microenvironment.Methods From April 2013 to October 2013,MSCs pretreated with inflammatory cytokine IL-1α （MSCs （IL-1α）） and its culture supernatants mixed with RM-1 cells,which origined from C57BL/6 mice,were subcutaneously administered in the armpit area of C57BL/6 or BALB/c mice to establish homologous or heterologous transplant animal mode and to detect the tumor growth.Meanwhile the influence of MSCs on the proliferation of spleen cells was detected in vitro.Results In homologous transplant model,the relative tumor weight of prostate cancer cells prtreated with MSCs and MSCs （IL-1α） and their culture supernatant were （3.4 ± 0.2）,（3.3 ±0.2）,（4.9±0.5）,and （5.2±0.6） g.The results were statistically significant （P＜0.05） compared with the control group （2.4±0.2） g.In heterologous model,the ratio of tumor formation of the pretreated groups were 50％,50％,80％ and 80％,respectively,compared with the control group of 0％.The results were statistically significant （P＜0.05）.In proliferation experiments of spleen cells,the number of spleen cell pretreated with IL-1α were significantly lower than that in control group and unpretreated group （P ＜ 0.05）.Conclusions MSCs pretreated with IL-1α could effectively promote the growth of prostate cancer cell in vivo.The reason may be due to inflammatory cytokines induce immune suppression of MSCs and then lead to immune escape of cancer cells.