结直肠癌细胞通过IL-33/ST2轴招募肥大细胞的研究

Colorectal cancer cells recruit mast cells via IL-33/ST2 axis

关键词:  结直肠癌  IL-33/ST2轴  肥大细胞  迁移  细胞因子

Key words:  colorectal cancer  IL-33/ST2 axis  mast cell  migration  cytokine

摘要:

目的 探讨结直肠癌细胞通过IL-33/ST2轴招募肥大细胞的作用机制。方法 收集结直肠癌组织及癌旁组织石蜡切片各15例，免疫组织荧光检测结肠癌及癌旁组织肥大细胞的浸润情况以及IL-33的表达量。利用细胞免疫荧光检测肥大细胞表面ST2受体的表达，Transwell细胞迁移实验观察IL-33、结直肠癌细胞条件培养液、IL-33+sST2（IL-33受体抑制剂）、结直肠癌细胞条件培养基+sST2条件下肥大细胞体外迁移能力的变化。将肥大细胞与结肠癌细胞共培养，RT-PCR检测肥大细胞细胞因子的表达。结果 相比于癌旁组织，结直肠癌组织的肥大细胞数量明显增多，IL-33的表达量也增加（P<0.001）。IL-33和结肠癌细胞条件培养基可以增强肥大细胞的迁移能力，而加入IL-33的抑制剂sST2后，迁移能力减弱（P<0.01）。共培养后的肥大细胞相比对照组，肥大细胞表达细胞因子IL-4、IL-6、IL-10和GM-CSF表达水平显著增加（P<0.05）。结论 结直肠癌细胞能够通过IL-33/ST2轴招募肥大细胞。

Abstract:

Objective To investigate whether colorectal cancer (CRC) cells recruit mast cells (MCs) via IL-33/ST2 axis. Methods The infiltration of MCs and the expression of IL-33 in CRC or adjacent tissues were determined by immunofluorescence histochemistry. Immunofluorescence staining was performed to test whether MCs expressed the IL-33 receptor ST2. Transwell assay was performed to detect the migration ability of MCs induced by IL-33 or conditioned medium (CM) of CRC cells with or without soluble ST2 (sST2, a decoy receptor). The expression of cytokines in MCs co-cultured with CRC cells was examined by using RT-qPCR. Results The infiltration of MCs and the expression of IL-33 increased in CRC tissues compared to adjacent tissues（P<0.001）. IL-33 and CRC CM enhanced the migration ability of MCs, and addition of sST2 suppressed this effect（P<0.01）. Furthermore, MCs co-cultured with CRC cells exhibited higher expression of IL-4, IL-6, IL-10 and GM-CSF than control groups（P<0.05）. Conclusion These results suggest that CRC cells could recruit mast cells via IL-33/ST2 axis.