CD98 marks a subpopulation of head and neck squamous cell carcinoma cells with stem cell properties
CD98 marks a subpopulation of head and neck squamous cell carcinoma cells with stem cell properties
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DOI：
10.1016/j.scr.2013.02.004
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发表时间：
2013-05-01
影响因子：
1.2
通讯作者：
Brakenhoff, Ruud H.
中科院分区：
文献类型：
--
作者：
Martens-de Kemp, Sanne R.;Brink, Arjen;Brakenhoff, Ruud H.
晚期头颈部鳞状细胞癌（HNSCC）患者通常接受同步化疗和放疗，但只有50%的患者治愈。治疗失败的一个可能的解释是癌症干细胞（CSC）的治疗抗性。除了常规使用的治疗剂之外，应用特异性靶向这些CSC的化合物可能会改善临床结果。我们证明，以前描述的单克隆抗体K984识别的CD98细胞表面蛋白，这是专门表达的细胞形成鳞状基底细胞层，鳞状干细胞所在的区域。此外，CD 98对CSC富集程序所需的蛋白水解酶具有高度耐药性。我们发现，与CD98（低）细胞相比，CD98（高）细胞能够在免疫缺陷小鼠中产生肿瘤，表明CD98（高）细胞具有干细胞特征。此外，CD98（高）亚群表达高水平的细胞周期控制和DNA修复基因，而CD98（低）部分显示的表达模式代表了形成肿瘤主体的分化程度更高的细胞。CD98是HNSCC中有希望的CSC富集标志物。我们的数据支持CSC在头颈癌中的概念以及这些细胞与治疗结果的潜在相关性。(C)2013爱思唯尔有限公司版权所有。
Patients with advanced head and neck squamous cell carcinomas (HNSCCs) are often treated with concomitant chemotherapy and radiotherapy, but only 50% is cured. A possible explanation for treatment failure is therapy resistance of the cancer stem cells (CSCs). The application of compounds specifically targeting these CSCs, in addition to routinely used therapeutics, would likely improve clinical outcome. We demonstrate that the previously described monoclonal antibody K984 recognizes the CD98 cell surface protein, which is specifically expressed by cells forming the squamous basal cell layer, the region where the squamous stem cells reside. Moreover, CD98 is highly resistant to the proteolytic enzymes required for CSC enrichment procedures. We show that CD98(high) cells, in contrast to CD98(low) cells, are able to generate tumors in immunodeficient mice, indicating that CD98(high) cells have stem cell characteristics. Furthermore, the CD98(high) subpopulation expresses high levels of cell cycle control and DNA repair genes, while the CD98(low) fraction shows expression patterns that represent the more differentiated cells forming the bulk of the tumor. CD98 is a promising CSC enrichment marker in HNSCC. Our data support the CSC concept in head and neck cancer and the potential relevance of these cells for treatment outcome. (C) 2013 Elsevier B.V. All rights reserved.