Molecular definition of breast tumor heterogeneity
Molecular definition of breast tumor heterogeneity
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DOI：
10.1016/j.ccr.2007.01.013
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发表时间：
2007-03-01
期刊：
影响因子：
50.3
通讯作者：
Polyak, Kornelia
中科院分区：
文献类型：
--
作者：
Shipitsin, Michail;Campbell, Lauren L.;Polyak, Kornelia
在正常人乳腺上皮和乳腺癌中存在具有干细胞样特性的细胞，但其分子特征和临床意义尚不清楚。我们使用先前与干细胞样特性相关的标记物，确定了从癌性和正常乳腺组织中纯化的细胞的基因表达和遗传特征。单个肿瘤的CD 24+和CD 44+细胞具有克隆相关性，但并不总是相同的。CD 44+细胞特异性基因包括许多已知的干细胞标志物，与患者生存率降低相关。TGF-β通路在CD 44+癌细胞中特别活跃，其抑制诱导更多的上皮表型。我们的数据表明CD 44+细胞的预后相关性和不同肿瘤细胞群体的治疗靶向。
Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.