CD44 and β1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins
CD44 and β1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins
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DOI：
10.1023/a:1026519016213
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发表时间：
2000-01-01
影响因子：
4
通讯作者：
Skubitz, APN
中科院分区：
文献类型：
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作者：
Casey, RC;Skubitz, APN
卵巢上皮癌通过肿瘤细胞植入腹膜腔的间皮细胞而扩散。本研究的目的是确定介导卵巢癌细胞向间皮细胞相关细胞外基质迁移的细胞-基质相互作用。通过流式细胞术分析人卵巢癌细胞系NIH：OVCAR 5和SKOV 3的细胞表面受体的表达。这些受体介导卵巢癌细胞向纤连蛋白、IV型胶原和层粘连蛋白迁移的能力被确定。针对β 1整合素亚基的单克隆抗体废除了两种细胞系向细胞外基质蛋白的迁移。针对α整合素亚单位的阻断性抗体提示卵巢癌细胞向纤连蛋白迁移主要是由5 β 1整合素、IV型胶原和层粘连蛋白介导的，其中5 β 1整合素、IV型胶原和层粘连蛋白分别与2 β 1整合素和6 β 1整合素成比例。这些结果表明，卵巢癌细胞迁移是由多种β 1整合素-基质相互作用。用阻断CD 44的透明质酸结合位点的抗CD 44单克隆抗体观察到细胞迁移的显著减少，但用在CD 44上的替代位点结合的抗体观察不到。完整的透明质酸和/或透明质酸寡聚体也抑制细胞迁移，表明CD 44-透明质酸相互作用提供了一种不依赖于整合素的卵巢癌细胞迁移控制机制。这些结果表明，卵巢癌细胞迁移是由整合素依赖性机制，涉及β 1整合素与细胞外基质蛋白的相互作用，和整合素独立的机制，涉及CD 44和透明质酸的相互作用。
Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial cells that line the peritoneal cavity. The aim of this study was to identify the cell-matrix interactions that mediate ovarian carcinoma cell migration toward components of the mesothelial cell-associated extracellular matrix. The human ovarian carcinoma cell lines NIH:OVCAR5 and SKOV3 were analyzed by flow cytometry for the expression of cell surface receptors. The ability of those receptors to mediate ovarian carcinoma cell migration toward fibronectin, type IV collagen, and laminin was determined. A monoclonal antibody against the beta1 integrin subunit abrogated the migration of both cell lines toward the extracellular matrix proteins. Blocking antibodies against alpha integrin subunits suggest that ovarian carcinoma cell migration toward fibronectin is primarily mediated by the proportional to5 beta1 integrin, type IV collagen by the proportional to2 beta1 integrin, and laminin by the proportional to6 beta1 integrin. These results suggest that ovarian carcinoma cell migration is regulated by multiple beta1 integrin-matrix interactions. Significant reduction of cell migration was observed with a monoclonal antibody against CD44 that blocks the hyaluronan-binding site of CD44, but not with an antibody that binds at an alternate site on CD44. Intact hyaluronan and/or hyaluronan oligomers also inhibited cell migration, suggesting that the CD44-hyaluronan interaction provides an integrin-independent mechanism of control for ovarian carcinoma cell migration. These results suggest that ovarian carcinoma cell migration is regulated by both integrin-dependent mechanisms, involving the interaction of beta1 integrins with extracellular matrix proteins, and an integrin-independent mechanism that involves the interaction of CD44 and hyaluronan.