Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors
Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors
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DOI：
10.1634/stemcells.2007-0440
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发表时间：
2008-02-01
期刊：
影响因子：
5.2
通讯作者：
Clarke, Michael F.
中科院分区：
文献类型：
--
作者：
Cho, Robert W.;Wang, Xinhao;Clarke, Michael F.
在人类乳腺癌中，当移植到免疫缺陷小鼠中时，表型不同的少数肿瘤发生（TG）癌细胞（有时称为癌症干细胞）群体驱动肿瘤生长。我们的目标是确定一个乳腺癌干细胞的小鼠模型，可能与人类乳腺癌的研究有关。为此，我们使用小鼠乳腺肿瘤病毒（MMTV）-Wnt-1小鼠的乳腺肿瘤。收获MMTV-Wnt-1乳腺肿瘤，解离成单细胞悬液，并通过流式细胞术在Thy 1、CD 24和CD 45上进行分选。然后将分选的细胞注射到受体背景FVB/NJ雌性同基因小鼠中。在检查的7个肿瘤中的6个中，Thy 1 + CD 24+癌细胞（占肿瘤细胞的约1% - 4%）与不符合该特征的肿瘤细胞（“非Thy 1 + CD 24+”）相比，高度富集了能够再生新肿瘤的细胞。所得肿瘤具有与原始肿瘤相似的表型多样性，并且在传代时以相似的方式表现。微阵列分析比较Thy 1 + CD 24+肿瘤细胞与非Thy 1 + CD 24+细胞，确定了一系列差异表达基因。这些差异表达基因的直系同源物预测了两个不同研究组的人类乳腺癌患者的生存率。这些研究表明，在MMTV-Wnt-1小鼠乳腺肿瘤中存在癌症干细胞区室，并且该模型在癌症干细胞研究中具有临床实用性。
In human breast cancers, a phenotypically distinct minority population of tumorigenic (TG) cancer cells (sometimes referred to as cancer stem cells) drives tumor growth when transplanted into immunodeficient mice. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to the study of human breast cancer. To do so, we used breast tumors of the mouse mammary tumor virus (MMTV)-Wnt-1 mice. MMTV-Wnt-1 breast tumors were harvested, dissociated into single-cell suspensions, and sorted by flow cytometry on Thy1, CD24, and CD45. Sorted cells were then injected into recipient background FVB/NJ female syngeneic mice. In six of seven tumors examined, Thy1+CD24+ cancer cells, which constituted approximately 1% - 4% of tumor cells, were highly enriched for cells capable of regenerating new tumors compared with cells of the tumor that did not fit this profile ("not-Thy1+CD24+"). Resultant tumors had a phenotypic diversity similar to that of the original tumor and behaved in a similar manner when passaged. Microarray analysis comparing Thy1+CD24+ tumor cells to not-Thy1+CD24+ cells identified a list of differentially expressed genes. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells.