Plasma Membrane Proteomics of Tumor Spheres Identify CD166 as a Novel Marker for Cancer Stem-like Cells in Head and Neck Squamous Cell Carcinoma
Plasma Membrane Proteomics of Tumor Spheres Identify CD166 as a Novel Marker for Cancer Stem-like Cells in Head and Neck Squamous Cell Carcinoma
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肿瘤球质膜蛋白质组学将 CD166 鉴定为头颈鳞状细胞癌中癌症干细胞样细胞的新标记物
DOI：
10.1074/mcp.m112.025460
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发表时间：
2013-11-01
影响因子：
7
通讯作者：
Zhang, Ping
中科院分区：
文献类型：
--
作者：
Yan, Ming;Yang, Xihu;Zhang, Ping
晚期头颈部鳞状细胞癌（HNSCC）患者的预后较差，目前可用的治疗，肿瘤复发是经常观察到的。特异性膜相关癌症干细胞（CSC）标志物的发现对于开发靶向这些CSC的新治疗策略至关重要。为了解决这个问题，我们建立了球体培养物来富集CSC，并将它们用于质膜蛋白质组学，以鉴定HNSCC球体的特异性膜特征。在包括总共376种鉴定的蛋白质的数据集中，200种是真正的膜蛋白。其中，123种蛋白质在相对于贴壁培养物的球体中至少上调或下调1.5倍。这些蛋白质包括细胞粘附分子、受体和转运蛋白。其中一些在wnt、整合素和TGF信号通路中起关键作用。当我们将我们的数据集与两个已发表的hESC膜蛋白特征进行比较时，我们发现所有三个数据库共有18个蛋白质。CD 166和CD 44是两种这样的蛋白。有趣的是，CD 166的表达，而不是公认的HNSCC CSC标志物CD 44的表达，与HNSCC的恶性行为显著相关。相对于CD 166（低）HNSCC细胞，CD 166（高）HNSCC细胞具有更大的体外成球能力和体内成瘤能力。肿瘤表达高水平CD 166的患者的临床结局显著差于肿瘤表达低水平CD 166的患者（队列1：96例，p = 0.040），而CD 44表达水平对HNSCC患者的临床结局仅有轻微影响（p = 0.078）。HNSCC肿瘤中的CD 166表达水平也与肿瘤复发率相关（队列2：104例，p = 0.016）。这项研究表明，CD 166是一个有价值的细胞表面标记物的富集HNSCC干细胞和质膜蛋白质组学是一个有前途的生物学工具，研究CSC的膜蛋白。Molecular & Cellular Proteomics 12：10.1074/mcp. M112.025460，3271-3284，2013.
Patients with advanced head and neck squamous cell carcinoma (HNSCC) have a poor prognosis with the currently available therapy, and tumor recurrence is frequently observed. The discovery of specific membrane-associated cancer stem cell (CSC) markers is crucial for the development of novel therapeutic strategies to target these CSCs. To address this issue, we established sphere cultures to enrich CSCs and used them for plasma membrane proteomics to identify specific membrane signatures of the HNSCC spheres. Of a dataset that included a total of 376 identified proteins, 200 were bona fide membrane proteins. Among them, 123 proteins were at least 1.5-fold up- or down-regulated in the spheres relative to the adherent cultures. These proteins included cell adhesion molecules, receptors, and transporter proteins. Some of them play key roles in wnt, integrin, and TGF signaling pathways. When we compared our dataset with two published hESC membrane protein signatures, we found 18 proteins common to all three of the databases. CD166 and CD44 were two such proteins. Interestingly, the expression of CD166, rather than that of the well-established HNSCC CSC marker CD44, was significantly related to the malignant behavior of HNSCC. Relative to CD166(low) HNSCC cells, CD166(high) HNSCC cells had a greater sphere-formation ability in vitro and tumor formation ability in vivo. Patients whose tumors expressed high levels of CD166 had a significantly poorer clinical outcome than those whose tumors expressed low levels of CD166 (cohort 1: 96 cases, p = 0.040), whereas the level of CD44 expression had only a marginal influence on the clinical outcome of patients with HNSCC (p = 0.078). The level of CD166 expression in HNSCC tumors was also associated with the tumor recurrence rate (cohort 2: 104 cases, p = 0.016). This study demonstrates that CD166 is a valuable cell surface marker for the enrichment of HNSCC stem cells and that plasma membrane proteomics is a promising biological tool for investigating the membrane proteins of CSCs. Molecular & Cellular Proteomics 12: 10.1074/mcp.M112.025460, 3271-3284, 2013.