A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer.
A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer.
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DOI：
10.1016/j.stem.2011.12.018
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发表时间：
2012-02-03
期刊：
影响因子：
23.9
通讯作者：
Wahl GM
中科院分区：
文献类型：
--
作者：
Spike BT;Engle DD;Lin JC;Cheung SK;La J;Wahl GM
乳腺干细胞群与乳腺癌相关的基因表达特征主要集中在成人组织。在这里，我们确定，分离和表征胎儿乳腺干细胞（fMaSC）状态，因为乳腺发生的侵入性和增殖过程类似于癌症进展的阶段。fMaSC频率在胚胎发生后期达到峰值，使得能够进行比成人组织更广泛的干细胞纯化。fMaSC是自我更新的、多能的，并且共表达多种乳腺谱系标志物。基因表达、移植和体外分析揭示了假定的自分泌和旁分泌调节机制，包括ErbB和FGF信号通路对fMaSC生长的影响。来自fMaSC和相关基质的表达谱表现出与基底样和Her2+内在乳腺癌亚型的显著相似性。我们的研究结果揭示了发育与癌症之间的重要联系，并为识别诊断，预后和治疗的新候选人提供了资源。
Gene expression signatures relating mammary stem cell populations to breast cancers have focused on adult tissue. Here, we identify, isolate and characterize the fetal mammary stem cell (fMaSC) state since the invasive and proliferative processes of mammogenesis resemble phases of cancer progression. fMaSC frequency peaks late in embryogenesis, enabling more extensive stem cell purification than achieved with adult tissue. fMaSCs are self-renewing, multipotent, and co-express multiple mammary lineage markers. Gene expression, transplantation, and in vitro analyses reveal putative autocrine and paracrine regulatory mechanisms including ErbB and FGF signaling pathways impinging on fMaSC growth. Expression profiles from fMaSCs and associated stroma exhibit significant similarities to basal-like and Her2+ intrinsic breast cancer subtypes. Our results reveal significant links between development and cancer and provide resources to identify new candidates for diagnosis, prognosis and therapy.