High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer
High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer
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DOI：
10.1016/j.ygyno.2005.03.016
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发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Santin, AD
中科院分区：
文献类型：
--
作者：
Bellone, S;Watts, K;Santin, AD
目的.评估和比较子宫内膜癌中白细胞介素-6（IL-6）的自分泌表达和产生，IL-6是一种多效细胞因子，参与体外和体内对细胞毒性药物的抗性和抗肿瘤免疫功能的抑制。应用实时荧光定量PCR技术检测了24例子宫内膜癌组织中IL-6基因的表达水平，包括14例子宫内膜样癌（EC）和10例子宫浆液性乳头状癌（USPC）以及正常对照子宫内膜细胞（NEC）。采用酶联免疫吸附试验（ELISA）检测了6种子宫内膜癌细胞（USPC和EC）分泌IL-6蛋白的情况。最后，检测了71例血清中IL-6的含量，其中包括20例健康妇女，19例良性腹部疾病，19例原发性食管癌，13例USPC患者。当与EC相比时，USPC中IL-6基因表达水平显著更高（通过RT-PCR的平均拷贝数分别为313 +/-55 vs. 53 11，USPC vs. EC：P < 0.01）。正常健康女性（范围0.01 - 21.23 pg/ml;平均3.1 pg/ml）和良性疾病患者（范围0.01-95.77 pg/ml;平均13.07 pg/ml）之间的IL-6血清浓度无统计学差异。与此相反，在EC患者中检测到显著更高水平的IL-6，（范围2.86-82.13 pg/ml;平均20.43 pg/ml）和UPSC患者（范围16.3-500.1 pg/ml;平均125.7 pg/ml）USPC组血清IL-6水平是EC组的6.1倍（P < 0.03）。因此，与原代EC（平均88 pg/ml，范围19 - 112 pg/ml/10（5）cells/48 h）相比，原代USPC细胞系（平均3121 pg/ml，范围1099 - 5017 pg/ml/10（5）cells/48 h）的IL-6分泌水平更高（P < 0.01）。IL-6在USPC中高度表达，并且在USPC患者的血清中以高浓度释放。IL-6可能是USPC的一种新型生物标志物。用于抑制IL-6表达或IL-6信号转导通路的药物可能对USPC非常有益。(c)2005年爱思唯尔公司All rights reserved.
Purpose. To evaluate and compare autocrine expression and production of interleukin-6 (IL-6), a pleiotropic cytokine involved in the resistance to cytotoxic agents and inhibition of anti-tumor immune function in endometrial carcinoma in vitro as well as in vivo.Patients and methods. IL-6 gene expression levels were evaluated in twenty-four primary endometrial tumors including 14 endometrioid carcinomas (EC) and 10 uterine serous papillary carcinoma (USPC) as well as in normal control endometrial cells (NEC) by real-time PCR. Secretion of IL-6 protein by 6 primary endometrial tumor cultures including USPC and EC was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) in vitro. Finally, IL-6 concentration in 71 serum samples including 20 apparently healthy women, 19 women with benign abdominal diseases, 19 women with primary EC, and 13 USPC patients was studied.Results. IL-6 gene expression levels were significantly higher in USPC when compared to EC (mean copy number by RT-PCR 313 +/- 55 vs. 53 11, USPC vs. EC, respectively: P < 0.01). IL-6 serum concentrations between normal healthy females (range 0.01 -21.23 pg/ml; mean 3.1 pg/ml) and benign disease patients (range 0.01-95.77 pg/ml; mean 13.07 pg/ml) were not statistically different. In contrast, significantly higher levels of IL-6 were detected in both patients with EC (range 2.86-82.13 pg/ml; mean 20.43 pg/ml) and patients with UPSC (range 16.3-500.1 pg/ml; mean 125.7 pg/ml) when compared to the healthy females (P < 0.01), with a mean serum IL-6 level in USPC patients 6.1-fold higher when compared to EC patients (P < 0.03). Accordingly, higher levels of IL-6 secretion were noted in primary USPC cell lines (mean 3121 pg/ml, range between 1099 and 5017 Pg/ml/10(5) cells/48 h) when compared to primary EC (mean 88, range between 19 and 112 pg/ml/10(5) cells/48 h) (P < 0.01) in vitro.Conclusions. IL-6 is highly expressed in USPC, and it is released in high concentration in the serum of USPC patients. IL-6 may be a novel biomarker for USPC. Drugs used to inhibit the expression of IL-6 or the IL-6 signal transduction pathway may potentially be highly beneficial in USPC. (c) 2005 Elsevier Inc. All rights reserved.