Puiffe Marie-Line, Le Page Cécile, Filali-Mouhim Abdelali, Zietarska Magdalena, Ouellet Véronique, Tonin Patricia N, Chevrette Mario, Provencher Diane M, Mes-Masson Anne-Marie
Centre de recherche du Centre hospitalier de l'Université de Montréal/Institut du cancer de Montréal, Montreal, Quebec, Canada.
Neoplasia. 2007 Oct;9(10):820-9. doi: 10.1593/neo.07472.
At least one third of all cases of epithelial ovarian cancer are associated with the production of ascites, although its effect on tumor cell microenvironment remains poorly understood. This study addresses the effect of the heterologous acellular fraction of ovarian cancer-derived ascites on a cell line (OV-90) derived from the chemotherapy-naïve ovarian cancer patient. Ascites were assayed for their effect on cell invasion, growth, and spheroid formation. When compared to either no serum or 5% serum, ascites fell into one of two categories: stimulatory or inhibitory. RNA from OV-90 cells exposed to selected ascites were arrayed on an Affymetrix HG-U133A GeneChip. A supervised analysis identified a number of differentially expressed genes and quantitative polymerase chain reaction validation based on OV-90 cells exposed to 54 independent ascites demonstrated that stimulatory ascites affected the expression of ISGF3G, TRIB1, MKP1, RGS4, PLEC1, and MOSPD1 genes. In addition, TRIB1 expression was shown to independently correlate with prognosis when its expression was ascertained in an independent set of primary cultures established from ovarian ascites. The data support the validity of the strategy to uncover molecular events that are associated with tumor cell behavior and highlight the impact of ascites on the cellular and molecular parameters of ovarian cancer.
至少三分之一的上皮性卵巢癌病例与腹水产生有关,尽管其对肿瘤细胞微环境的影响仍知之甚少。本研究探讨了卵巢癌来源腹水的异源无细胞成分对来自未经化疗的卵巢癌患者的细胞系(OV-90)的影响。检测了腹水对细胞侵袭、生长和球体形成的作用。与无血清或5%血清相比,腹水分为两类:刺激性或抑制性。将暴露于选定腹水的OV-90细胞的RNA阵列于Affymetrix HG-U133A基因芯片上。一项监督分析鉴定出一些差异表达基因,基于暴露于54份独立腹水的OV-90细胞进行的定量聚合酶链反应验证表明,刺激性腹水影响ISGF3G、TRIB1、MKP1、RGS4、PLEC1和MOSPD1基因的表达。此外,当在从卵巢腹水中建立的一组独立原代培养物中确定TRIB1表达时,其表达显示与预后独立相关。这些数据支持了揭示与肿瘤细胞行为相关分子事件策略的有效性,并突出了腹水对卵巢癌细胞和分子参数的影响。