Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells.
Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells.
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DOI：
10.18632/oncotarget.2698
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Papagerakis S
中科院分区：
文献类型：
--
作者：
Desiderio V;Papagerakis P;Tirino V;Zheng L;Matossian M;Prince ME;Paino F;Mele L;Papaccio F;Montella R;Papaccio G;Papagerakis S
口腔鳞状细胞癌(OSCC)是一种高死亡率的侵袭性恶性肿瘤。口腔鳞状细胞癌治疗面临的主要挑战包括治疗耐药性的产生和远处转移的早期形成。肿瘤干细胞(CSCs)在这两种病理机制中都扮演着重要角色。岩藻糖化活性增加和岩藻糖化多糖表达增加，如唾液酸路易斯X(SLeX)，与肿瘤的侵袭和转移有关。然而，岩藻糖基化在CSCs中的作用尚未阐明。我们使用球体培养技术获得了富含CSC的细胞群，并将球体与贴壁细胞进行了比较。我们发现，与贴壁的颗粒相比，颗粒更高水平表达CSCs和转移标志，更具侵袭性和致瘤性，对顺铂/辐射的抵抗力更强。通过剪切流分析，我们发现岩藻糖基转移酶FUT3和FUT6在球体中高度上调，SLeX表达增加，粘附性增加。抑制岩藻糖基化对牙周血球的形成和口腔CSCs的侵袭有负面影响。这些结果证实了球体富含CSC，岩藻糖化对CSC的入侵起着至关重要的作用。此外，SLeX可能在CSC转移中起关键作用。因此，抑制岩藻糖基化可用于阻断CSCs和转移扩散。
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with high mortality rates. Major challenges for OSCC management include development of resistance to therapy and early formation of distant metastases. Cancer stem cells (CSCs) have emerged as important players in both pathologic mechanisms. Increased fucosylation activity and increased expression of fucosylated polysaccharides, such as Sialyl Lewis X (SLex), are associated with invasion and metastasis. However, the role of fucosylation in CSCs has not been elucidated yet. We used the spheroid culture technique to obtain a CSC-enriched population and compared orospheres with adherent cells. We found that orospheres expressed markers of CSCs and metastasis at higher levels, were more invasive and tumorigenic, and were more resistant to cisplatin/radiation than adherent counterparts. We found fucosyltransferases FUT3 and FUT6 highly up-regulated, increased SLex expression and increased adhesion by shear flow assays in orospheres. Inhibition of fucosylation negatively affected orospheres formation and invasion of oral CSCs. These results confirm that orospheres are enriched in CSCs and that fucosylation is of paramount importance for CSC invasion. In addition, SLex may play a key role in CSC metastasis. Thus, inhibition of fucosylation may be used to block CSCs and metastatic spread.
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DOI：
10.1016/j.biocel.2009.09.010
发表时间：
2010-01-01
影响因子：
4
作者：
Carvalho, A. S.;Harduin-Lepers, A.;Reis, C. A.
通讯作者：
Reis, C. A.
影响因子：
3.5
作者：
Higai, Koji;Miyazaki, Noriko;Matsumoto, Kojiro
通讯作者：
Matsumoto, Kojiro
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ
影响因子：
64.5
作者：
Kim, CFB;Jackson, EL;Jacks, T
通讯作者：
Jacks, T
DOI：
10.1186/1758-3284-2-5
发表时间：
2010-02-22
期刊：
Head & neck oncology
影响因子：
--
作者：
Liebertz DJ;Lechner MG;Masood R;Sinha UK;Han J;Puri RK;Correa AJ;Epstein AL
通讯作者：
Epstein AL