Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma.
Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma.
复制标题
将CD146鉴定为富含肿瘤能力的标记物，揭示了原代人肉瘤的目标途径。
DOI：
10.18632/oncotarget.5375
复制
发表时间：
2015-11-24
期刊：
影响因子：
--
通讯作者：
Alman BA
中科院分区：
文献类型：
--
作者：
Wei Q;Tang YJ;Voisin V;Sato S;Hirata M;Whetstone H;Han I;Ailles L;Bader GD;Wunder J;Alman BA
肿瘤增殖细胞（TPC）被认为是驱动癌症发生、进展和复发的因素。这些细胞的特征在于增强的致瘤性和自我更新。在原发性人肉瘤中鉴定此类细胞的能力依赖于肿瘤侧群（SP）细胞的染料排斥能力。在这里，我们进行了高通量的细胞表面抗原筛选，发现CD 146在SP群体中富集。体内系列移植试验表明，CD146+细胞是高度致瘤性的，能够自我更新，从而富集TPC群体。此外，从CD 146+群体中去除SP细胞表明CD 146+细胞和SP细胞是不同的且重叠的TPC群体。CD 146+和SP细胞的基因表达谱显示，在这两个群体中，多个途径通常上调。抑制这些上调的途径之一，Notch信号传导，显着降低肿瘤生长和自我更新。我们的数据表明，CD 146是一种有效的细胞表面标记物，用于富集原发性人肉瘤中的TPC。靶向TPC中的差异激活通路可能为治疗肉瘤提供新的治疗策略。
Tumor-propagating cells (TPCs) are believed to drive cancer initiation, progression and recurrence. These cells are characterized by enhanced tumorigenicity and self-renewal. The ability to identify such cells in primary human sarcomas relies on the dye exclusion ability of tumor side population (SP) cells. Here, we performed a high-throughput cell surface antigen screen and found that CD146 is enriched in the SP population. In vivo serial transplantation assays showed that CD146+ cells are highly tumorigenic, capable of self-renewal and thus enriches for the TPC population. In addition, depletion of SP cells from the CD146+ population show that CD146+ cells and SP cells are a distinct and overlapping TPC populations. Gene expression profiling of CD146+ and SP cells revealed multiple pathways commonly upregulated in both of these populations. Inhibition of one of these upregulated pathways, Notch signaling, significantly reduced tumor growth and self-renewal. Our data demonstrate that CD146 is an effective cell surface marker for enriching TPCs in primary human sarcomas. Targeting differentially activated pathways in TPCs may provide new therapeutic strategies for treating sarcoma.