Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.
Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.
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DOI：
10.1158/0008-5472.can-08-3343
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发表时间：
2009-04-01
期刊：
影响因子：
11.2
通讯作者：
Knutson KL
中科院分区：
文献类型：
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作者：
Santisteban M;Reiman JM;Asiedu MK;Behrens MD;Nassar A;Kalli KR;Haluska P;Ingle JN;Hartmann LC;Manjili MH;Radisky DC;Ferrone S;Knutson KL
乳腺癌干细胞（BCSC）假说认为，乳腺癌是从一个单一的肿瘤起始细胞与干细胞的性质，但这些细胞的来源是不清楚的。我们以前观察到，诱导对上皮性乳腺癌的免疫反应导致体内肿瘤的T细胞依赖性生长，其细胞经历了上皮间质转化（EMT）。由此产生的间充质肿瘤细胞具有CD 24 −/loCD 44+表型，与BCSC一致。在本研究中，我们发现EMT是由CD 8 T细胞诱导的，所产生的肿瘤具有BCSC的特征，包括强致瘤性，重建上皮肿瘤的能力，以及对药物和放射的抵抗力增强。相反，分层癌症干细胞的假设，这表明乳腺癌是由居民组织干细胞的转化，我们的研究结果表明，EMT可以产生BCSC表型。这些发现具有与疾病进展和复发相关的几个重要意义。
The breast cancer stem cell (BCSC) hypotheses suggest that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source of these cells is unclear. We previously observed that induction of an immune response against an epithelial breast cancer led in vivo to the T cell-dependent outgrowth of a tumor, the cells of which had undergone epithelial to mesenchymal transition (EMT). The resulting mesenchymal tumor cells had a CD24−/loCD44+ phenotype, consistent with BCSCs. In the present study, we found that EMT was induced by CD8 T cells and the resulting tumors had characteristics of BCSCs, including potent tumorigenicity, ability to re-establish an epithelial tumor, and enhanced resistance to drugs and radiation. In contrast to the hierarchal cancer stem cell hypothesis which suggests that breast cancer arises from the transformation of a resident tissue stem cell, our results show that EMT can produce the BCSC phenotype. These findings have several important implications related to disease progression and relapse.