Cell membrane glycosylation mediates the adhesion, migration, and invasion of ovarian carcinoma cells

Cell membrane glycosylation mediates the adhesion, migration, and invasion of ovarian carcinoma cells
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DOI:
10.1023/a:1022670501667
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发表时间:
2003-01-01
影响因子:
4
通讯作者:
Skubitz, APN
Skubitz, APN
中科院分区:
医学3区
文献类型:
--
作者:
Casey, RC;Oegema, TR;Skubitz, APN

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我们之前已经表明,卵巢癌细胞与间皮细胞单层的粘附以及向纤连蛋白、IV型胶原和层粘连蛋白的迁移部分是由CD44介导的,CD44是一种已知会影响肿瘤细胞功能的蛋白多糖。本研究的目的是确定细胞膜糖基化在卵巢癌细胞转移能力中的作用。用糖苷酶处理 NIH:OVCAR5 细胞,以去除细胞表面分子中的碳水化合物部分。评估了处理的细胞粘附到细胞外基质成分或间皮细胞单层、向细胞外基质蛋白迁移以及通过基质胶侵入的能力。我们观察到不同碳水化合物部分的丢失导致卵巢癌细胞粘附、迁移和/或侵袭细胞外基质成分或间皮细胞单层的改变。 NIH:OVCAR5 细胞的基因阵列分析揭示了多种蛋白聚糖的表达,包括 Syndecan 4、核心蛋白聚糖和基底膜聚糖。在从患者获得的组织样本中,与正常卵巢相比,在原发性卵巢癌肿瘤和继发性转移瘤中观察到蛋白多糖基因表达的改变。综上所述,这些结果表明卵巢癌细胞蛋白多糖影响细胞粘附、迁移和侵入细胞外基质成分和间皮细胞单层的能力。因此,几种蛋白多糖的碳水化合物修饰可能介导卵巢癌中继发性肿瘤生长的形成和扩散。
We have previously shown that ovarian carcinoma cell adhesion to mesothelial cell monolayers and migration toward fibronectin, type IV collagen, and laminin is partially mediated by CD44, a proteoglycan known to affect the functional abilities of tumor cells. The purpose of this study was to determine the role of cell membrane glycosylation in the metastatic abilities of ovarian carcinoma cells. NIH:OVCAR5 cells were treated with glycosidases to remove carbohydrate moieties from molecules on the cells' surface. The ability of the treated cells to adhere to extracellular matrix components or mesothelial cell monolayers, migrate toward extracellular matrix proteins, and invade through Matrigel was assessed. We observed that the loss of different carbohydrate moieties resulted in altered ovarian carcinoma cell adhesion, migration, and/or invasion toward extracellular matrix components or mesothelial cell monolayers. Gene array analysis of NIH:OVCAR5 cells revealed the expression of several proteoglycans, including syndecan 4, decorin, and perlecan. In tissue samples obtained from patients, altered proteoglycan gene expression was observed in primary ovarian carcinoma tumors and secondary metastases, compared to normal ovaries. Taken together, these results suggest that ovarian carcinoma cell proteoglycans affect the cells' ability to adhere, migrate, and invade toward extracellular matrix components and mesothelial cell monolayers. Thus, the carbohydrate modifications of several proteoglycans may mediate the formation and spread of secondary tumor growth in ovarian carcinoma.