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首页> 外文期刊>Neurosurgery >Overexpression of hyaluronan synthase-2 reduces the tumorigenic potential of glioma cells lacking hyaluronidase activity.
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Overexpression of hyaluronan synthase-2 reduces the tumorigenic potential of glioma cells lacking hyaluronidase activity.

机译:透明质酸合酶2的过表达减少了缺乏透明质酸酶活性的神经胶质瘤细胞的致瘤潜力。

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OBJECTIVE: The interactions of CD44 with hyaluronan are thought to be crucial for tumor cell attachment to the extracellular matrix, migration, and invasion. For migration to occur, however, the interactions between hyaluronan and cell surface receptors need to be transient. Hyaluronidases may facilitate the degradation of hyaluronan bound to the cell surface and thus reduce the interactions of the cells with the matrix, whereas the overproduction of hyaluronan in the absence of hyaluronidase activity may prevent cells from proliferating or invading normal surrounding tissue. METHODS: We analyzed the effects in vitro and in vivo of hyaluronan synthase-2 (HAS2) overexpression on a murine glioma cell line that is deficient in hyaluronidase activity. In addition, we evaluated the expression levels of HAS and hyaluronidase genes in human glioma cell lines and in glioma specimens. RESULTS: Increased hyaluronan synthesis had no effect on the in vitro proliferation of the cells but diminished their in vivo growth rate. Several human glioma cell lines were found to overexpress hyaluronan synthases, but they did so in conjunction with hyaluronidase Hyal2 and MGEA5 expression. Similarly, all glioblastomas multiforme expressed hyaluronidases MGEA5 and Hyal2. CONCLUSION: The data suggest that an increased synthesis of hyaluronan by astrocytoma cells is only promoting tumor cell growth in vivo if the cells express hyaluronidases as well.
机译:目的:CD44与透明质酸的相互作用被认为对于肿瘤细胞附着于细胞外基质,迁移和侵袭至关重要。然而,为了发生迁移,透明质酸和细胞表面受体之间的相互作用需要是瞬时的。透明质酸酶可以促进结合到细胞表面的透明质酸的降解,从而减少细胞与基质的相互作用,而在缺乏透明质酸酶活性的情况下透明质酸的过量生产可以阻止细胞增殖或侵袭正常的周围组织。方法:我们分析了透明质酸合酶2(HAS2)过度表达对小鼠透明质酸酶活性不足的小鼠神经胶质瘤细胞系的影响。此外,我们评估了人类胶质瘤细胞系和神经胶质瘤标本中HAS和透明质酸酶基因的表达水平。结果:透明质酸合成的增加对细胞的体外增殖没有影响,但降低了它们的体内生长速率。发现几种人类神经胶质瘤细胞系过表达透明质酸合酶,但它们与透明质酸酶Hyal2和MGEA5的表达一起表达。同样,所有胶质母细胞瘤均表达透明质酸酶MGEA5和Hyal2。结论:数据表明星形胶质细胞瘤细胞增加的透明质酸合成仅在体内也表达透明质酸酶时才促进肿瘤细胞的生长。

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