CD44 and β1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells
CD44 and β1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells
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DOI：
10.1016/s0002-9440(10)65406-5
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发表时间：
1999-05-01
影响因子：
6
通讯作者：
Skubitz, APN
中科院分区：
文献类型：
--
作者：
Lessan, K;Aguiar, DJ;Skubitz, APN
卵巢上皮癌通过肿瘤细胞植入腹腔内的间皮细胞进行扩散，本研究的目的是鉴定卵巢癌细胞与间皮细胞相互作用的粘附分子，用流式细胞术分析人卵巢癌细胞系SKOV3和MH:OVCAR5以及人腹膜间皮细胞系LP9细胞中CD44和β 1整合素亚基的表达。在体外粘附实验中，将LP9细胞培养成融合单层，并监测放射标记卵巢癌细胞在潜在抑制剂存在的情况下粘附间皮单层的能力。每个细胞系通过颗粒排除试验评估细胞周围基质的存在。针对β 1整合素亚基的单克隆抗体（MAb）可显著降低SKOV3细胞对LP9细胞的粘附，而CD44 MAb可显著抑制NIH:OVCAR5对LP9细胞的粘附。LP9细胞产生透明质酸（CD44的配体）和几种细胞外基质分子（β 1整合素异二聚体的配体），这些结果表明CD44和β 1整合素异二聚体可能在介导卵巢癌细胞与间皮细胞的粘附中起作用。
Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial cells lining the peritoneal cavity, The aim of this study was to identify the adhesion molecules involved in the interaction of ovarian carcinoma cells with mesothelial cells, The human ovarian carcinoma cell lines SKOV3 and MH:OVCAR5 as well as LP9 cells, a human peritoneal mesothelial cell line, were analyzed by flow cytometry for the expression of CD44 and the beta 1 integrin subunit. An in vitro adhesion assay was developed whereby LP9 cells were grown as confluent monolayers, and radiolabeled ovarian carcinoma cells were monitored for their ability to adhere to the mesothelial monolayer in the presence of potential inhibitors. Each cell line was evaluated for the presence of a pericellular matrix by a particle exclusion assay. A monoclonal antibody (MAb) against the beta 1 integrin subunit significantly reduced the adhesion of SKOV3 cells to LP9 cells, whereas NIH:OVCAR5 adhesion to LP9 cells was significantly inhibited by a CD44 MAb. The LP9 cells produced both hyaluronic acid (a Ligand for CD44) as well as several extracellular matrix molecules (ligands for the beta 1 integrin heterodimers), These results suggest that both CD44 and the beta 1 integrin heterodimers may play a role in mediating the adhesion of ovarian carcinoma cells to mesothelial cells.