肿瘤相关巨噬细胞和Sema4D与胃癌浸润转移的关系

Tumor-associated macrophages and Semaphorin4D are related to the invasion and metastasis of gastric carcinoma

目的:研究肿瘤相关巨噬细胞(TAMs)对人胃癌SGC-7901细胞系生物学功能的影响。方法 :采用佛波酯(PMA)、白细胞介素IL-4和IL-13体外诱导人M2型巨噬细胞,细胞免疫荧光鉴定TAMs。Transwell非接触式共培TAMs和胃癌SGC-7901细胞,侵袭实验、迁移实验检测肿瘤相关巨噬细胞(TAMs)对胃癌SGC-7901细胞侵袭和迁移的影响,酶联免疫吸附法(ELISA)检测实验组和空白对照组胃癌SGC-7901细胞上清中分泌型Sema4D的变化。结果:细胞免疫荧光鉴定M2型巨噬细胞诱导成功;在Transwell共培养体系中,TAMs共培养的胃癌SGC-7901细胞形态学发生改变;Transwell侵袭实验、迁移实验表明,细胞侵袭转移力增强(P<0.01)。与TAMs共培养的胃癌SGC-7901细胞的上清液分泌型Sema4D蛋白明显增多,较空白对照组差异有统计学意义(1224.13±29.43比637.15±33.84,P<0.01)。结论 :TAMs可促进胃癌细胞的浸润转移,其原因可能与分泌型Se m a4D蛋白的表达上调有关。

Objective： To study the impact of tumor associated macrophages （TAMs） on the biological function of SGC-7901 gastric cancer cells and explore the possible reasons. Methods：Human mononuclear cells THP-1 was induced in to M2-type macrophages form with phorbol 12-myristate 13-acetate（PMA）, interleukin（IL）-4 and interleukin（IL）-13. Establish the co-culture system of SGC-7901 gastric cancer cells and TAMs. Invasion and migration assays were used to examine the effect of tumor-associated macrophages on migration and invasion in SGC-7901 gas- tric cancer cells. ELISA assay was used to detect the variation of Sema4D in the blank control group and the co-culture system supernatant, Results： TAMs were successfully induced and were con- firmed by immunofluorescence. After being cultured in the co-culture system, the SGC-7901 gastric cancer cells morphological changed, the results of transwell assay showed the invasion and migration ability of cells were obviously increased（P〈0.01）. The ELtSA assay indicated： compared with control group, the co-culture system supernatant showed a significant increase of secreted Sema4D （1224.13 ±29.43 vs 637.15 ±33.84, P〈0.01）. Conclusion： TAMs promoted SGC-7901 gastric cancer cells invasion and migration. The induced migration and invasion could be due to the up-reg- ulation of Sema4D.