The glycocalyx maintains a cell surface pH nanoenvironment crucial for integrin-mediated migration of human melanoma cells
The glycocalyx maintains a cell surface pH nanoenvironment crucial for integrin-mediated migration of human melanoma cells
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DOI：
10.1007/s00424-009-0694-7
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发表时间：
2009-10-01
影响因子：
4.5
通讯作者：
Stock, Christian
中科院分区：
文献类型：
--
作者：
Kraehling, Hermann;Mally, Sabine;Stock, Christian
糖萼由蛋白聚糖、糖蛋白、糖胺聚糖、相关血浆蛋白和可溶性糖胺聚糖组成，覆盖所有真核细胞的表面。它介导特定的识别事件，调节配体-受体相互作用等生物过程，并被认为可以影响肿瘤转移。在这里，我们研究了黑色素瘤细胞迁移是否需要糖萼。我们通过抑制翻译后 N-糖基化或通过酶消化 N-糖苷来减少人黑色素瘤细胞的糖萼。糖萼的部分破坏使黑色素瘤细胞迁移减少了 60%。它伴随着通常围绕迁移细胞的特征性 pH 纳米环境的瓦解。通过刺激 Na+/H+ 交换器 NHE1 的活性来恢复这种 pH 分布，即使在没有完整糖萼的情况下也能挽救细胞迁移。与敲低 β(1)-整合素表达相比，部分去除糖萼的效果表明糖萼、整合素和细胞表面 pH 纳米环境之间存在密切的功能相关性。我们得出结论，糖萼是肿瘤细胞迁移所必需的。它可以稳定细胞表面 pH 纳米环境，从而实现粘附受体和细胞外基质之间的 pH 依赖性相互作用。
The glycocalyx consists of proteoglycans, glycoproteins, glycosaminoglycans, associated plasma proteins, and soluble glycosaminoglycans and covers the surface of all eukaryotic cells. It mediates specific recognition events, modulates biological processes such as ligand-receptor interactions, and has been proposed to affect tumor metastasis. Here, we studied whether the glycocalyx is required for melanoma cell migration. We diminished the glycocalyx of human melanoma cells by inhibiting post-translational N-glycosylation or by enzymatic digestion of the N-glycosides. This partial destruction of the glycocalyx reduced melanoma cell migration by up to 60%. It was accompanied by the disintegration of a characteristic pH nanoenvironment typically surrounding migrating cells. Restoring this pH profile by stimulating the activity of the Na+/H+ exchanger NHE1 rescued cell migration even in the absence of an intact glycocalyx. The effects of partially removing the glycocalyx compared to those of knocking down beta(1)-integrin expression points to a close functional correlation between glycocalyx, integrins, and cell surface pH nanoenvironment. We conclude that the glycocalyx is required for tumor cell migration. It stabilizes the cell surface pH nanoenvironment allowing a concerted pH-dependent interaction of adhesion receptors and extracellular matrix.