Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models
Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models
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DOI：
10.1073/pnas.1006732107
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发表时间：
2010-10-19
影响因子：
11.1
通讯作者：
Clarke, Michael F.
中科院分区：
文献类型：
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作者：
Liu, Huiping;Patel, Manishkumar R.;Clarke, Michael F.
为了研究乳腺癌干细胞（BCSCs）在转移中的作用，我们使用患者肿瘤标本构建了人源肿瘤小鼠原位乳腺癌模型，并标记了光学报告融合基因。这些模型重现了以往模型未涵盖的人类癌症特征，特别是自发性转移，为乳腺肿瘤的发生和进展研究提供了一个有用的平台。通过非侵入性成像方法，在体内可以追踪到少至10个稳定标记的乳腺癌干细胞，从而能够研究早期肿瘤生长和自发性转移。乳腺癌干细胞成像方面的这些进展表明，来自原发肿瘤和肺转移灶的CD44（+）细胞中肿瘤起始细胞高度富集。我们的转移性癌症模型与非侵入性成像技术相结合，构成了一种综合方法，可用于剖析转移性癌症干细胞（MCSCs）扩散的分子机制，探索针对MCSCs的治疗策略，或者评估个体患者的肿瘤细胞并预测对治疗的反应。
To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44(+) cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy.