Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides
Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides
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DOI：
10.1007/s10585-010-9363-7
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发表时间：
2011-02-01
影响因子：
4
通讯作者：
Ricciardelli, Carmela
中科院分区：
文献类型：
--
作者：
Ween, Miranda P.;Hummitzsch, Katja;Ricciardelli, Carmela
含有透明质酸（HA）和桃聚糖的细胞周围基质的组装是间充质细胞增殖和迁移的先决条件。在这项研究中，我们研究了重组versican是否可以诱导卵巢癌细胞（OVCAR-3、OVCAR-5和SKOV-3）形成细胞周基质，并促进其在体外对腹膜细胞的运动、侵袭和粘附。我们还确定了小HA寡糖是否可以阻断花青素诱导的细胞外基质形成和转移癌细胞行为。只有重组versican和HA联合处理才能导致OVCAR-5和SKOV-3细胞形成细胞外基质，而缺乏HA受体CD44的OVCAR-3细胞则不能形成细胞外基质。重组versican和HA处理后，在抓伤和趋化实验中，OVCAR-5和SKOV-3细胞的运动性显著增加。Versican和HA也促进了SKOV-3和OVCAR-5细胞的侵袭，但对OVCAR-3细胞没有影响。我们已经证明，外源性HA显著增加了OVCAR-5和SKOV-3对腹膜细胞的粘附，但versican治疗并没有进一步增加这种粘附。小HA低聚物（6-10双糖）能够显著阻断OVCAR-5细胞形成细胞周围基质，以及重组versican诱导的细胞运动性和侵袭性的增加。在存在和不存在外源性HA的情况下，HA低聚物也显著阻断OVCAR-5对腹膜细胞的粘附。CD44中和抗体在versican和HA存在的情况下抑制细胞周围基质的形成以及OVCAR-5细胞的运动和侵袭，证明了CD44对versican和HA介导的作用的依赖性。我们得出结论，卵巢癌细胞获得HA/versican细胞周基质增加了它们的转移潜力。透明质酸低聚物可以阻断这一机制，是卵巢癌传播的有希望的抑制剂。
The assembly of pericellular matrix containing hyaluronan (HA) and versican has been shown to be a prerequisite for proliferation and migration of mesenchymal cells. In this study, we investigated whether treatment with recombinant versican could induce the formation of a pericellular matrix by ovarian cancer cells (OVCAR-3, OVCAR-5, and SKOV-3) and promote their motility, invasion, and adhesion to peritoneal cells in vitro. We also determined whether versican-induced pericellular matrix formation and metastatic cancer cell behavior could be blocked by small HA oligosaccharides. Only combined treatment with recombinant versican and HA resulted in pericellular matrix formation by OVCAR-5 and SKOV-3 but not by OVCAR-3 cells, which lack the HA receptor, CD44. The motility of OVCAR-5 and SKOV-3 cells was significantly increased in scratch wound and chemotaxis assays following treatment with recombinant versican and HA. Versican and HA also promoted invasion of SKOV-3 and OVCAR-5 cells but had no effect on OVCAR-3 cells. We have demonstrated that exogenous HA significantly increased OVCAR-5 and SKOV-3 adhesion to peritoneal cells but adhesion was not further increased by versican treatment. Small HA oligomers (6-10 disaccharides) were able to significantly block formation of pericellular matrix by OVCAR-5 cells, as well as the increased motility and invasion induced by recombinant versican. HA oligomers also significantly blocked OVCAR-5 adhesion to peritoneal cells both in the presence and absence of exogenous HA. The dependence of CD44 for the versican and HA mediated effects were demonstrated by the inhibition of pericellular matrix formation as well as motility and invasion of OVCAR-5 cells following treatment with CD44 neutralizing antibody in the presence of versican and HA. We conclude that the acquisition of a HA/versican pericellular matrix by ovarian cancer cells increases their metastatic potential. HA oligomers can block this mechanism and are promising inhibitors of ovarian cancer dissemination.