The Density and Length of Filopodia Associate with the Activity of Hyaluronan Synthesis in Tumor Cells
The Density and Length of Filopodia Associate with the Activity of Hyaluronan Synthesis in Tumor Cells
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DOI：
10.3390/cancers12071908
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发表时间：
2020-07-01
期刊：
影响因子：
5.2
通讯作者：
Rilla, Kirsi
中科院分区：
文献类型：
--
作者：
Kyykallio, Heikki;Oikari, Sanna;Rilla, Kirsi
丝状足是一种多功能的手指状质膜突起，具有成束的肌动蛋白丝，几乎存在于所有类型的细胞中。透明质酸的合成活性诱导丝状体生长已经有一段时间了。然而，由于研究这些细长而脆弱的结构的技术挑战，到目前为止还没有进行定量分析来表明它们与透明质酸合成的关系。在这项工作中，我们全面地解决了丝状面性状的直接量化，首次覆盖了一系列具有不同水平透明质酸合成的人类癌细胞系的长度和密度测量。通过透明质酸合成酶3 （HAS3）和透明质酸受体CD44过表达，以及甘露糖、4-甲基菊酮（4-MU）和葡萄糖胺处理，控制透明质酸的合成和质膜结合。这项工作的结果表明，丝状足的生长与透明质酸合成水平有关，但不依赖于CD44的表达。结果证实了癌细胞丝状足的丰度和长度与透明质酸合成活性有关的假设。
Filopodia are multifunctional finger-like plasma membrane protrusions with bundles of actin filaments that exist in virtually all cell types. It has been known for some time that hyaluronan synthesis activity induces filopodial growth. However, because of technical challenges in the studies of these slender and fragile structures, no quantitative analyses have been performed so far to indicate their association with hyaluronan synthesis. In this work we comprehensively address the direct quantification of filopodial traits, covering for the first time length and density measurements in a series of human cancer cell lines with variable levels of hyaluronan synthesis. The synthesis and plasma membrane binding of hyaluronan were manipulated with hyaluronan synthase 3 (HAS3) and hyaluronan receptor CD44 overexpression, and treatments with mannose, 4-methylumbelliferone (4-MU), and glucosamine. The results of this work show that the growth of filopodia was associated with the levels of hyaluronan synthesis but was not dependent on CD44 expression. The results confirm the hypothesis that abundance and length of filopodia in cancer cells is associated with the activity of hyaluronan synthesis.