子宫内膜癌肿瘤微环境内IGFBP-3表达及其对肿瘤侵袭能力的影响  

The expression of IGFBP-3 in endometrial tumor microenvironment and its effects on cancer cell invasion

作　　者：李艳辉[1] 高颖[1] 汪宏波[1] 金志珊[1] 

机构地区：[1]华中科技大学附属协和医院妇产科,武汉430022

出　　处：《现代妇产科进展》2014年第6期422-426,共5页Progress in Obstetrics and Gynecology

摘　　要：目的:探讨子宫内膜癌肿瘤微环境内IGFBP-3表达与肿瘤-间质相互作用的关系,以及IGFBP-3表达对子宫内膜癌侵袭能力的影响。方法:免疫组化法检测子宫内膜癌、正常子宫内膜组织中IGFBP-3的表达情况。肿瘤相关成纤维细胞(CAF)、正常内膜成纤维细胞(NF)与子宫内膜癌Ishikawa细胞在Transwell小室内共培养,RT-PCR、ELISA法检测IGFBP-3表达水平的改变。Transwell侵袭实验评估IGFBP-3表达改变对Ishikawa细胞侵袭能力的影响。结果:子宫内膜癌组织中IGFBP-3表达显著低于正常子宫内膜组织(P<0.01)。CAF、NF与Ishikawa细胞共培养后,两种间质成纤维细胞中IGFBP-3 mRNA表达水平均显著下降(P<0.01);而在Ishikawa细胞,CAF可使其IGFBP-3 mRNA表达显著降低(P<0.01),但NF对其无显著影响(P>0.05)。CAF、NF均能促进Ishikawa细胞的侵袭能力;与单Ishikawa细胞组和NF+Ishikawa共培养组相比,CAF共培养能显著增加Ishikawa细胞的侵袭能力(113.33±8.50 vs 65.17±10.23、75.33±8.21,P<0.01)。而加入外源性重组人IGFBP-3后,能显著抑制CAF的促侵袭作用。结论:子宫内膜癌肿瘤与间质相互作用可导致肿瘤微环境内IGFBP-3表达下降,而肿瘤微环境IGFBP-3表达的改变与子宫内膜癌的生长、侵袭和转移密切相关。Objective： To assess the expression of IGFBP-3 in endometrial cancer micro environment and to explore its association with tumor-stroma interaction and cancer cell invasion. Methods： IGFBP-3 protein expression in endometrial cancer and endometrium were analyzed by immunohistochemistry. Cancer-associated fibroblasts（ CAF）,normal endometrial fibroblasts（ NF） were respectively cocultured with Ishikawa cells in the Transwell,and IGFBP-3mRNA and protein expression were detected by RT-PCR and ELISA. Transwell invasion assay was taken to assess the effects of IGFBP-3 and CAF on Ishikawa cell invasion. Results： IGFBP-3 protein expression in endometrial cancer was significantly lower than that in endometriun（ P〈0. 01）. After CAF and NF co-cultured with Ishikawa cells,IGFBP-3 mRNA expression decreased in these two stromal fibroblasts（ P〈0. 01）. For Ishikawa cells,CAF can reduced its IGFBP-3 mRNA expression（ P〈0. 01）,but no such effect of NF was seen（ P〉0. 05）. CAF,NF can promote the Ishikawa cells invasion. rhIGFBP-3 significantly inhibited the pro-invasion effect of the CAF. Conclusion： Tumor stroma interaction can reduce the IGFBP-3 expression of the endometrial cancer. In the cancer microenvironment,the down-regulation of IGFBP-3 expression is associated with endometrial cancer growth,invasion and metastasis.

关 键 词：子宫内膜癌 肿瘤间质相互作用 IGFBP-3 侵袭能力 

分 类 号：R737.33[医药卫生—肿瘤]