肿瘤微环境促进子宫内膜癌细胞分泌雌激素

目的:筛选子宫内膜癌微环境中促进子宫内膜癌细胞雌激素分泌的细胞因子,并探讨相关机制。方法:提取子宫内膜癌间质细胞,用双重免疫荧光法进行鉴定。检测子宫内膜癌细胞(RL95-2、HEC-1A和HEC-1B)与间质细胞共培养和单独培养模式下,培养液上清雌激素浓度和肿瘤细胞芳香化酶的表达情况。用细胞因子芯片筛选2种模式下差异性表达的细胞因子,并用real-time PCR进行验证。结果:成功提取肿瘤间质细胞(波形蛋白为阳性)。共培养组上清雌激素浓度和肿瘤细胞中芳香化酶mRNA表达量均高于单独培养组(P<0.01)。共培养组上清中生长分化因子-15(GDF-15)的表达高于单独培养组,10 ng/mL的GDF-15可显著上调子宫内膜癌细胞中芳香化酶的表达(P<0.01)。结论:子宫内膜癌细胞与间质细胞共培养情况下,子宫内膜癌细胞中芳香化酶的表达,进而促进间质细胞雌激素浓度的合成,其中子宫内膜癌细胞中GDF-15可能发挥重要作用。

Tumor microenvironment promoting estrogen secretion in endometrial cancer

Objective: To screen the cytokines promoting estrogen secretion in endometrial cancer cells in tumor microenvironment, and to study the related mechanism. Methods: Stromal cells of endometrial carcinoma were isolated and identified by double immunofluorescence. The concentrations of estrogen and expression of aromatase in endometrial cancer cells (RL95-2, HEC-1A, and HEC-1B) were measured under the co-culture with stromal cells and individual culture modes. The differentially expressed cytokines were screened by cytokine chip and further verified by real-time PCR. Results: The vimentin in the extracted cells was positive, which indicated the extraction of tumor stromal cells was successful. The concentration of estrogen in the supernatant and the expression of aromatase in tumor cells in the co-culture group were significantly higher than that in the individual culture group (P<0.01). The expression of growth differentiation factor-15 (GDF-15) in the supernatant of co-culture group was significantly higher than that in the individual culture group (P<0.01), and the expression of aromatase in endometrial cancer cells was significantly upregulated by 10 ng/mL GDF-15(P<0.01). Conclusions: Under the condition of co-culture of endometrial cancer cells and stromal cells, the expression of aromatase is significantly increased in endometrial cancer cells, which promotes the estrogen secretion in stromal cells, and GDF-15 in endometrial carcinoma cell might play an important role.