Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers
Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers
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DOI：
10.1016/j.ygyno.2003.12.034
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发表时间：
2004-04-01
影响因子：
4.7
通讯作者：
Skubitz, APN
中科院分区：
文献类型：
--
作者：
Burleson, KM;Casey, RC;Skubitz, APN
客观的。卵巢癌细胞在晚期疾病患者的腹膜腔中形成多细胞聚集体或球体。目前腹水球体是非粘附性的范式使其对卵巢癌扩散的贡献尚不清楚。在这里，从卵巢癌患者的腹水中获得的球状体的特征在于它们粘附腹膜腔中遇到的分子的能力，目的是确定它们促进卵巢癌扩散的潜力。方法。从 11 名 III 期或 IV 期卵巢癌患者的腹水中回收了球状体。对每个腹水球体样品进行细胞外基质（ECM）蛋白和人间皮细胞单层的粘附测定。随后，进行抑制测定以鉴定所涉及的细胞受体。结果。大多数腹水样本对纤连蛋白和 I 型胶原蛋白有适度的粘附，对 IV 型胶原蛋白和层粘连蛋白的粘附力降低。针对β1整合素亚基的单克隆抗体部分抑制了这种粘附。腹水球体也粘附于透明质酸。此外，球体粘附在活的、但不是固定的人间皮细胞单层上，并且这种粘附部分是由β1整合素介导的。结论。腹水的细胞内容物通常被认为是非粘附性的，但我们的研究结果首次表明患者来源的腹水球体可以通过β1整联蛋白粘附到间皮细胞外基质，这表明球体在卵巢癌的传播中不应被忽视。 (C) 2004 Elsevier Inc. 保留所有权利。
Objective. Ovarian carcinoma cells form multicellular aggregates, or spheroids, in the peritoneal cavity of patients with advanced disease. The current paradigm that ascites spheroids are non-adhesive leaves their contribution to ovarian carcinoma dissemination undefined. Here, spheroids obtained from ovarian carcinoma patients' ascites were characterized for their ability to adhere to molecules encountered in the peritoneal cavity, with the goal of establishing their potential to contribute to ovarian cancer spread.Methods. Spheroids were recovered from the ascites fluid of 11 patients with stage III or stage IV ovarian carcinoma. Adhesion assays to extracellular matrix (ECM) proteins and human mesothelial cell monolayers were performed for each of the ascites spheroid samples. Subsequently, inhibition assays were performed to identify the cell receptors involved.Results. Most ascites samples adhered moderately to fibronectin and type I collagen, with reduced adhesion to type IV collagen and laminin. Monoclonal antibodies against the beta1 integrin subunit partially inhibited this adhesion. Ascites spheroids also adhered to hyaluronan. Additionally, spheroids adhered to live, but not fixed, human mesothelial cell monolayers, and this adhesion was partially mediated by beta1 integrins.Conclusions. The cellular content of the ascites fluid has often been considered non-adhesive, but our findings are the first to suggest that patient-derived ascites spheroids can adhere to mesothelial extracellular matrix via beta1 integrins, indicating that spheroids should not be ignored in the dissemination of ovarian cancer. (C) 2004 Elsevier Inc. All rights reserved.