HYALURONIC-ACID CD44H INTERACTION INDUCES CELL DETACHMENT AND STIMULATES MIGRATION AND INVASION OF HUMAN GLIOMA-CELLS IN-VITRO
HYALURONIC-ACID CD44H INTERACTION INDUCES CELL DETACHMENT AND STIMULATES MIGRATION AND INVASION OF HUMAN GLIOMA-CELLS IN-VITRO
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DOI：
10.1002/ijc.2910630325
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发表时间：
1995-11-03
影响因子：
6.4
通讯作者：
MERZAK, A
中科院分区：
文献类型：
--
作者：
KOOCHEKPOUR, S;PILKINGTON, GJ;MERZAK, A
胶质瘤是人类固有的脑肿瘤的主要形式，其侵袭特性的潜在机制尚不清楚。我们已经报道了CD44在体外这种行为中起着重要的作用。在本工作中，我们研究了其配体透明质酸(HA)在8个人脑胶质瘤细胞系侵袭中的作用。我们发现，HA通过与其高亲和力受体CD44H的相互作用而介导细胞脱离。使用8微米孔隙率的聚碳酸酯过滤器跨井，我们证明了HA强烈刺激所有8种细胞系的迁移。这种作用被CD44H单抗(MAb)部分抵消，提示CD44H以及其他HA受体参与了这一过程。此外，在体外侵袭实验中，在Matrigel中加入不断增加的HA浓度，导致胶质瘤细胞系侵袭倾向的显著增加。此外，CD44H单抗的阻断实验表明，CD44H和其他受体与HA相互作用，促进细胞体外侵袭。我们的结果表明，HA在体外通过与CD44H和其他HA受体相互作用而诱导细胞脱离、刺激迁移和促进侵袭。这些效应可以通过使用特异性HA受体抗体来预防。(C)1995年Wiley-Liss，Inc.
The mechanisms underlying the invasive properties of gliomas, the major form of intrinsic brain tumours in humans, are poorly understood. We have reported that CD44 plays an important role in this behavior in vitro. In the present work, we investigated the role of its ligand, hyaluronic acid (HA), in invasion in 8 human glioma cell lines. We found that HA mediates cell detachment via its interaction with its high affinity receptor, CD44H. Using 8 mu m porosity polycarbonate filter transwells, we demonstrate that HA strongly stimulates migration in all 8 cell lines. This effect was found to be partially counteracted by a CD44H monoclonal antibody (MAb), suggesting the involvement of CD44H, as well as other HA receptors, in this process. Furthermore, incorporation of increasing concentrations of HA in Matrigel in an in vitro invasion assay resulted in a substantial increase in the invasive propensity of the glioma cell lines. Moreover, blocking experiments with the CD44H MAb suggest that CD44H and other receptors interact with HA to promote cell invasion in vitro. Our results show that HA induces cell detachment, stimulates migration and promotes invasion via its interaction with CD44H and other HA receptors in vitro. These effects could be prevented by use of specific HA receptor antibodies. (C) 1995 Wiley-Liss, Inc