Vitronectin and Its Receptors Partly Mediate Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium in vitro

Vitronectin and Its Receptors Partly Mediate Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium in vitro
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DOI:
10.1159/000152941
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发表时间:
2008-01-01
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影响因子:
--
通讯作者:
Carreiras, Franck
Carreiras, Franck
中科院分区:
其他
文献类型:
--
作者:
Heyman, Loraine;Kellouche, Sabrina;Carreiras, Franck

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上皮性卵巢癌细胞通过植入腹腔腹膜间皮表面转移。导致这种植入的粘附分子尚不清楚。本研究的目的是研究玻璃体连接蛋白(Vn)及其受体α (v)整合素和尿激酶纤溶酶原激活剂受体(uPAR)在卵巢腺癌细胞(IGROV1和SKOV3细胞系)与间皮细胞(MeT-5A细胞系和原代培养)相互作用中的作用。对于所有细胞系,免疫荧光染色显示整个细胞表面和细胞周围薄的连续沉积物中存在Vn。Vn受体在细胞-细胞接触部位的招募也被发现。我们开发了两种不同的方法来评估体外细胞-细胞粘附使用肿瘤和间皮细胞共培养。两种黏附实验都显示卵巢癌细胞有很强的能力优先粘附于间皮细胞间连接处。使用抗vn -、- α (v)-整合素和- upar -阻断抗体或环肽cRGDfV可显著抑制卵巢癌细胞与间皮细胞的粘附。这些结果证明了卵巢癌细胞在体外结合腹膜间皮的能力,并强烈表明Vn及其受体参与了这一关键事件。版权所有2008 S. Karger AG,巴塞尔
Epithelial ovarian cancer cells metastasize by implanting onto the peritoneal mesothelial surface of the abdominal cavity. Adhesive molecules that lead to this implantation remain unclear. The aim of our study was to focus on the role of vitronectin (Vn) and its receptors, alpha(v) integrins and urokinase plasminogen activator receptor (uPAR), in the interactions of ovarian adenocarcinoma cells (IGROV1 and SKOV3 cell lines) with mesothelial cells (MeT-5A cell line and primary cultures). For all cell lines, immunofluorescence staining disclosed the presence of Vn over the whole cell surface and in thin continuous deposits underlining the cell periphery. Recruitment of Vn receptors to cell-cell contact sites was also revealed. We developed two distinct methods for the evaluation of in vitro cell-cell adhesion using cocultures of the tumor and mesothelial cells. Both adhesion assays revealed a strong ability of ovarian cancer cells to adhere preferentially to mesothelial intercellular junctions. Adhesion of ovarian carcinoma cells to mesothelial cells was significantly inhibited using anti-Vn-, -alpha(v)-integrin- and -uPAR-blocking antibodies or cyclic peptide cRGDfV. These results evidence the ability of ovarian carcinoma cells to bind to peritoneal mesothelium in vitro and strongly suggest that Vn and its receptors contribute to this crucial event. Copyright (C) 2008 S. Karger AG, Basel.