Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer.
Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer.
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DOI：
10.1155/2015/989070
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发表时间：
2015
影响因子：
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通讯作者：
Bourguignon LY
中科院分区：
文献类型：
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作者：
Shiina M;Bourguignon LY
我们确定，人头颈癌细胞（HSC-3细胞系）包含一个亚群显示癌症干细胞（CSC）的属性，是非常致瘤性。具体来说，我们研究了不同大小的透明质酸（HA）（例如，5 kDa、20 kDa、200 kDa或700 kDa-HA大小）在调节这些CSC中起作用。首先，我们观察到200 kDa-HA（而不是其他大小的HA）优先诱导某些干细胞标志物表达，导致这些细胞的自我更新和克隆形成。进一步的分析表明，200 kDa-HA选择性地刺激这些CSC中一组microRNA（最明显的是miR-10 b）的表达。200 kDa-HA还刺激了这些CSC中生存蛋白（cIAP-1）的表达，导致顺铂耐药性。此外，我们的结果表明，抗miR-10抑制剂不仅降低了存活蛋白的表达，而且还增加了200 kDa-HA处理的CSC的化学敏感性。这些发现有力地支持了以下论点：200 kDa-HA在miR-10产生中起关键作用，导致CSC中存活蛋白上调和化学抗性。总之，我们的研究结果表明，某些大小的HA（例如，200 kDa-HA）可能有助于CSC功能的形成，导致肿瘤细胞存活和头颈癌进展中的化学抗性。
We determined that human head and neck cancer cells (HSC-3 cell line) contain a subpopulation displaying cancer stem cell (CSC) properties and are very tumorigenic. Specifically, we investigated whether different sizes of hyaluronan (HA) (e.g., 5 kDa, 20 kDa, 200 kDa, or 700 kDa-HA-sizes) play a role in regulating these CSCs. First, we observed that 200 kDa-HA (but not other sizes of HA) preferentially induces certain stem cell marker expression resulting in self-renewal and clonal formation of these cells. Further analyses indicate that 200 kDa-HA selectively stimulates the expression of a panel of microRNAs (most noticeably miR-10b) in these CSCs. Survival protein (cIAP-1) expression was also stimulated by 200 kDa-HA in these CSCs leading to cisplatin resistance. Furthermore, our results indicate that the anti-miR-10 inhibitor not only decreases survival protein expression, but also increases chemosensitivity of the 200 kDa-HA-treated CSCs. These findings strongly support the contention that 200 kDa-HA plays a pivotal role in miR-10 production leading to survival protein upregulation and chemoresistance in CSCs. Together, our findings suggest that selective activation of oncogenic signaling by certain sizes of HA (e.g., 200 kDa-HA) may be instrumental in the formation of CSC functions leading to tumor cell survival and chemoresistance in head and neck cancer progression.