CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma.
CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma.
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DOI：
10.18632/oncotarget.2269
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发表时间：
2014-08-30
期刊：
影响因子：
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通讯作者：
Sunwoo JB
中科院分区：
文献类型：
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作者：
Murillo-Sauca O;Chung MK;Shin JH;Karamboulas C;Kwok S;Jung YH;Oakley R;Tysome JR;Farnebo LO;Kaplan MJ;Sirjani D;Divi V;Holsinger FC;Tomeh C;Nichols A;Le QT;Colevas AD;Kong CS;Uppaluri R;Lewis JS Jr;Ailles LE;Sunwoo JB
头颈部鳞状细胞癌（SCCHN）中的肿瘤起始细胞（TIC）的最佳特征是其表面表达CD 44。虽然有很大的兴趣，在确定战略，以针对这一群体，没有这些细胞的标记已被发现是功能上的活性。在这里，我们研究了正常人口腔上皮干细胞的标志物CD 271的表达。我们表明CD 271的表达仅限于CD 44+细胞的一个子集。使用异种移植试验，我们表明，CD 44 + CD 271+亚群包含最多的致瘤细胞。CD 271功能的丧失导致细胞周期的G2-M期阻滞，并对这些细胞在体内引发肿瘤形成的能力产生深远的负面影响。与重组NGF孵育导致Erk的磷酸化增强，提供了CD 271具有功能活性的额外证据。最后，SCCHN细胞与CD 271抗体的孵育导致Erk磷酸化减少和体内肿瘤形成减少。因此，我们的数据是第一个证明，CD 271更具体地确定在SCCHN中的CD 44+隔室中的TIC亚群，并且该受体是一种功能活性和靶向分子。
Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.