斯钙素 1 与卵巢肿瘤发生。
Stanniocalcin 1 and ovarian tumorigenesis.
机构信息
Department of Pathology, Unit 85, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
出版信息
J Natl Cancer Inst. 2010 Jun 2;102(11):812-27. doi: 10.1093/jnci/djq127. Epub 2010 May 18.
BACKGROUND
Stanniocalcin 1 (STC1) is a secreted glycoprotein hormone. High expression of STC1 has been associated with several cancers including ovarian cancer, but its role in the development of ovarian cancer is not clear.
METHODS
We used five human ovarian epithelial cancer cell lines (OVCA420, OVCA432, OVCA433, SKOV3, and HEY), immortalized human ovarian surface epithelial cells (T29 and T80), ovarian cancer tissues from 342 patients, serum from 73 ovarian cancer patients and from58 control subjects, and 116 mice, with six or eight per group. Protein expression was assessed. Cells overexpressing STC1 protein were generated by ectopic expression of human STC1 cDNA. STC1 expression was silenced by using small interfering RNA against STC1. Cell proliferation, migration, colony formation, and apoptosis were assessed. Xenograft tumor growth in mice was studied. Neutralizing anti-STC1 antibody was used to inhibit STC1 function. All statistical tests were two-sided.
RESULTS
STC1 protein expression was higher in all human ovarian cancer cell lines examined than in immortalized human ovarian epithelial cell lines, higher in ovarian cancer tissue than in normal ovarian tissue (P < .001), and higher in serum from ovarian cancer patients than from control subjects (P = .021). Ovarian cancer cells with STC1 overexpression, compared with corresponding control cells, had increased cell proliferation, migration, and colony formation in cell culture and increased growth of xenograft tumors in mice. These activities in normal or malignant ovarian cells with STC1 overexpression, compared with control cells, were also accompanied by increased expression of cell cycle regulatory proteins and antiapoptotic proteins but decreased cleavage of several caspases. Within 24 hours of treatment, apoptosis in cultures of HEY ovarian cancer cells treated with neutralizing anti-STC1 monoclonal antibody was higher (17.3% apoptotic cells) than that in cultures treated with mouse IgG control cells (4.4%) (12.9% difference, 95% confidence interval = 11.6% to 14.2%).
CONCLUSIONS
STC1 protein may be involved in ovarian tumorigenesis.
背景
Stanniocalcin 1（STC1）是一种分泌型糖蛋白激素。STC1 的高表达与包括卵巢癌在内的几种癌症有关，但它在卵巢癌发展中的作用尚不清楚。
方法
我们使用了五种人卵巢上皮癌细胞系（OVCA420、OVCA432、OVCA433、SKOV3 和 HEY）、永生化人卵巢表面上皮细胞（T29 和 T80）、来自 342 名患者的卵巢癌组织、来自 73 名卵巢癌患者和 58 名对照者的血清，以及每组 6 或 8 只的 116 只小鼠。评估了蛋白表达。通过过表达人 STC1 cDNA 生成过表达 STC1 蛋白的细胞。通过针对 STC1 的小干扰 RNA 沉默 STC1 表达。评估细胞增殖、迁移、集落形成和细胞凋亡。研究了小鼠中的异种移植肿瘤生长。使用中和抗-STC1 抗体抑制 STC1 功能。所有统计检验均为双侧。
结果
在所有检查的人卵巢癌细胞系中，STC1 蛋白表达均高于永生化人卵巢上皮细胞系，在卵巢癌组织中高于正常卵巢组织（P<0.001），在卵巢癌患者血清中高于对照者（P=0.021）。与相应对照细胞相比，过表达 STC1 的卵巢癌细胞在细胞培养中具有更高的细胞增殖、迁移和集落形成能力，以及在小鼠中的异种移植肿瘤生长更快。与对照细胞相比，过表达 STC1 的正常或恶性卵巢细胞中的这些活性还伴随着细胞周期调节蛋白和抗凋亡蛋白表达增加，但几种半胱天冬酶的切割减少。在治疗后 24 小时内，用中和抗-STC1 单克隆抗体处理的 HEY 卵巢癌细胞培养物中的凋亡（17.3%凋亡细胞）高于用鼠 IgG 对照细胞处理的培养物（4.4%）（12.9%差异，95%置信区间=11.6%至 14.2%）。
结论
STC1 蛋白可能参与卵巢肿瘤发生。
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