Progestin suppresses matrix metalloproteinase production in endometrial cancer
Progestin suppresses matrix metalloproteinase production in endometrial cancer
复制标题
DOI：
10.1016/s0090-8258(03)00089-1
复制
发表时间：
2003-05-01
影响因子：
4.7
通讯作者：
Salamonsen, LA
中科院分区：
文献类型：
--
作者：
Di Nezza, LA;Jobling, T;Salamonsen, LA
目标.子宫内膜癌（EC）是少数几种在过度激素刺激和恶性转化之间存在明确关系的癌症之一。在这项研究中，我们分析了雌激素和孕激素对原代EC细胞和EC细胞系中基质金属蛋白酶（MMP-9和MMP-2）产生的影响。MMPs通过包括细胞外基质降解和一系列分子（包括生长因子和细胞因子）的加工的机制参与癌症侵袭。从三名因I级子宫内膜腺癌接受子宫切除术的癌症患者和两名接受与EC无关的手术的患者收集的活检组织中分离细胞。将这些细胞加上EC细胞系石川和HEC-1A在没有激素的情况下或与醋酸甲羟孕酮（MPA）、雌二醇（E-2）或这些激素的组合一起培养。明胶和反向酶谱法分别用于分析培养基中的MMPs和TIMPs。RT-PCR检测类固醇受体的表达。细胞系与原代细胞在分泌的MMP的范围和丰度上不同。用MPA处理显著减少了原代EC癌和基质细胞的proMMP-9、proMMP-2和MMP-2释放。单独使用E-2或MPA + E-2处理对MMP表达没有显著影响。原代EC和基质细胞也显示孕酮B受体亚型的丢失。EC细胞保留了孕酮对MMPs的抑制作用，这在正常子宫内膜细胞中可见。这些数据提供了一个合理的使用resistin治疗早期I级子宫内膜癌的治疗。(C)2003 Elsevier Science（美国）。All rights reserved.
Objectives. Endometrial carcinoma (EC) is one of the few cancers where there is a clear relationship between excessive hormone stimulation and malignant transformation. In this study we have analyzed the effects of the female sex steroids estrogen and progesterone on matrix metalloproteinases (MMP-9 and -2) production in primary EC cells and EC cell lines. MMPs are implicated in cancer invasion via mechanisms including extracellular matrix degradation and the processing of a range of molecules, including growth factors and cytokines.Methods. Cells were isolated from biopsies collected from three cancer patients undergoing hysterectomy for grade I endometrial adenocarcinoma and two patients undergoing procedures unrelated to EC. These cells plus the EC cell lines Ishikawa and HEC-1A were cultured without hormones or with medroxyprogesterone acetate (MPA), estradiol (E-2), or these hormones in combination. Gelatin and reverse zymography were used to analyze MMPs and TIMPs, respectively, in culture medium. RT-PCR was used to characterize steroid receptor expression.Results. Cell lines differed from primary cells in the range and abundance of MMPs secreted. Treatment with MPA significantly reduced proMMP-9, proMMP-2, and MMP-2 release from primary EC cancer and stromal cells. Treatment with E-2 alone or MPA + E-2 had no significant effect on MMP expression. Primary EC and stromal cells also showed a loss of the progesterone B receptor isoform.Conclusion. EC cells retain the suppression of MMPs by progesterone, seen in normal endometrial cells. These data provide a rationale for the use of progestin therapy in the treatment of early stage grade I endometrial carcinomas. (C) 2003 Elsevier Science (USA). All rights reserved.