Department of Genetics, Biology and Biochemistry, University of Turin Medical School, Turin, Italy.
J Natl Cancer Inst. 2010 Aug 4;102(15):1160-77. doi: 10.1093/jnci/djq256. Epub 2010 Jul 16.
CD157, an ADP-ribosyl cyclase-related cell surface molecule, regulates leukocyte diapedesis during inflammation. Because CD157 is expressed in mesothelial cells and diapedesis resembles tumor cell migration, we investigated the role of CD157 in ovarian carcinoma.
We assayed surgically obtained ovarian cancer and mesothelial cells and both native and engineered ovarian cancer cell lines for CD157 expression using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), and for adhesion to extracellular matrices, migration, and invasion using cell-based assays. We investigated invasion of human peritoneal mesothelial cells by serous ovarian cancer cells with a three-dimensional coculture model. Experiments were performed with or without CD157-blocking antibodies. CD157 expression in tissue sections from ovarian cancer patients (n = 88) was examined by immunohistochemistry, quantified by histological score (H score), and categorized as at or above or below the median value of 60, and compared with clinical parameters. Statistical tests were two-sided.
CD157 was expressed by ovarian cancer cells and mesothelium, and it potentiated the adhesion, migration, and invasion of serous ovarian cancer cells through different extracellular matrices. CD157-transfected ovarian cancer cells migrated twice as much as CD157-negative control cells (P = .001). Blockage of CD157 inhibited mesothelial invasion by serous ovarian cancer cells in a three-dimensional model. CD157 was expressed in 82 (93%) of the 88 epithelial ovarian cancer tissue specimens. In serous ovarian cancer, patients with CD157 H scores of 60 or greater had statistically significantly shorter disease-free survival and overall survival than patients with lower CD157 H scores (CD157 H score > or =60 vs <60: median disease-free survival = 18 months, 95% confidence interval [CI] = 5.92 to 30.07 vs unreached, P = .005; CD157 H score > or =60 vs <60: median overall survival = 45 months, 95% CI = 21.21 to 68.79 vs unreached, P = .024). Multivariable Cox regression showed that CD157 is an independent prognostic factor for recurrence (hazard ratio of disease recurrence = 3.01, 95% CI = 1.35 to 6.70, P = .007) and survival (hazard ratio of survival = 3.44, 95% CI = 1.27 to 9.31, P = .015).
CD157 plays a pivotal role in the control of ovarian cancer cell migration and peritoneal invasion, and it may be clinically useful as a prognostic tool and therapeutic target.
CD157 是一种 ADP-ribosyl cyclase 相关的细胞表面分子，可调节炎症期间白细胞的渗出。由于 CD157 在间皮细胞中表达，并且渗出类似于肿瘤细胞迁移，因此我们研究了 CD157 在卵巢癌中的作用。
我们使用流式细胞术和逆转录-聚合酶链反应 (RT-PCR) 检测手术获得的卵巢癌和间皮细胞以及天然和工程化的卵巢癌细胞系中 CD157 的表达，并使用细胞基础测定法检测细胞对细胞外基质的粘附、迁移和侵袭。我们使用三维共培养模型研究了浆液性卵巢癌细胞对人腹膜间皮细胞的侵袭。实验在有或没有 CD157 阻断抗体的情况下进行。使用免疫组织化学检查 88 例卵巢癌患者组织切片中的 CD157 表达，通过组织学评分 (H 评分) 进行定量，并分为高于或低于中位数 60 的类别，并与临床参数进行比较。统计检验为双侧。
CD157 由卵巢癌细胞和间皮细胞表达，并通过不同的细胞外基质增强了浆液性卵巢癌细胞的粘附、迁移和侵袭。与 CD157 阴性对照细胞相比，转染 CD157 的卵巢癌细胞迁移的速度快了一倍 (P =.001)。阻断 CD157 抑制了三维模型中浆液性卵巢癌细胞对间皮细胞的侵袭。在 88 例上皮性卵巢癌组织标本中，82 例 (93%) 表达 CD157。在浆液性卵巢癌中，H 评分≥60 的患者的无病生存和总生存时间明显短于 H 评分较低的患者 (H 评分≥60 vs <60：无病生存中位数 = 18 个月，95%置信区间 [CI] = 5.92 至 30.07 个月 vs 未达到，P =.005；H 评分≥60 vs <60：总生存中位数 = 45 个月，95%CI = 21.21 至 68.79 个月 vs 未达到，P =.024)。多变量 Cox 回归显示 CD157 是复发的独立预后因素 (疾病复发的危险比 = 3.01，95%CI = 1.35 至 6.70，P =.007) 和生存 (生存的危险比 = 3.44，95%CI = 1.27 至 9.31，P =.015)。
CD157 在控制卵巢癌细胞迁移和腹膜侵袭中发挥关键作用，它可能作为一种临床有用的预后工具和治疗靶点。
