ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas.
ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas.
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DOI：
10.18632/oncotarget.5782
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发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Nör JE
中科院分区：
文献类型：
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作者：
Adams A;Warner K;Pearson AT;Zhang Z;Kim HS;Mochizuki D;Basura G;Helman J;Mantesso A;Castilho RM;Wicha MS;Nör JE
一个小的细胞亚群的特征是增加的致瘤潜力，自我更新和分化成构成肿瘤块的细胞的能力，已经在一些（但不是所有）肿瘤类型中表征。这些独特的细胞，称为癌症干细胞，被认为是这些肿瘤中肿瘤进展的驱动因素。这项工作的目的是了解癌症干细胞是否在涎腺粘液表皮样癌的肿瘤发生中发挥功能性作用。在这里，我们研究了假定的癌症干细胞标志物（ALDH，CD 10，CD 24，CD 44）的表达在原发性人类粘液表皮样癌的免疫荧光，在体外salisphere测定，在免疫缺陷小鼠体内致瘤性测定。与ALDHlowCD 44 low细胞相比，以ALDH活性和CD 44表达水平（ALDHhighCD 44 high）高水平分选的人粘液表皮样癌细胞（UM-HMC-1、UM-HMC-3A、UM-HMC-3B）在体外一致地形成原发性和继发性盐球，并显示出增强的体内致瘤潜力（定义为肿瘤可触知的时间，可触知后的肿瘤生长）。按CD 10/CD 24和CD 10/CD 44分选的细胞显示不同的唾液球形成趋势，但体内致瘤潜力始终较低。最后，当评价不同的细胞系时，按CD 44/CD 24分选的细胞在盐球形成和致瘤潜力测定中显示不一致的结果。总的来说，这些数据表明，唾液腺粘液表皮样癌含有一个小群体的癌症干细胞与增强的致瘤潜力，其特征是高ALDH活性和CD 44表达。这些结果表明，粘液表皮样癌患者可能受益于消融这些高致瘤性细胞的治疗。
A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDHhighCD44high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDHlowCD44low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.