2012年10月30日 讯 /生物谷BIOON/ --在以前的研究中，科学家们只知道乳腺中的一种类型的祖细胞。在一项新的研究中，来自英国癌症研究院剑桥研究所的研究人员在乳腺中鉴定出至少两类被称作祖细胞的早期细胞。不同于干细胞：它能够分化为任何类型的细胞并且持续进行细胞分裂，祖细胞只能够进行有限次细胞分裂。不同的祖细胞可能解释着为何存在着不同类型的乳腺癌。这项新的研究发现揭示出不同乳腺癌起源的线索，并且为有助于开发出潜在的新药物靶标。相关研究结果刊登在Breast Cancer Research期刊上。
研究人员发现一类被称作雌激素阳性祖细胞(oestrogen positive progenitor)的祖细胞含有雌激素受体。这种受体蛋白接受来自雌激素的信号。另一类被称作雌激素阴性祖细胞的祖细胞缺乏这种受体。
雌激素阳性祖细胞在低水平雌激素和黄体酮的环境---如绝经后女性的乳腺组织---中更好地存活下来。这提示着绝经后女性所患的乳腺瘤可能是由这类祖细胞产生的，不过还需开展进一步的研究来证实这一点。
雌激素阴性祖细胞的遗传指纹(genetic fingerprint)类似于一种侵袭性的乳腺癌，即基底样乳腺癌(basal-like breast cancer)，因此这类祖细胞更可能影响较为年轻的女性。这提示着这种乳腺癌可能是由这类雌激素阴性祖细胞产生的。
论文通信作者John Stingl说，“这种激动人心的发现揭示出乳腺要比科学家们起初所认为的更加复杂。发现新类型的祖细胞可能解释着为何存在不同类型的乳腺癌，以及为何年轻和年老的女性往往患上不同类型的乳腺癌。在未来，它也可能提供新的起点来诊断和治疗这种疾病。”(生物谷Bioon.com)
doi: 10.1186/bcr3334
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Phenotypic and functional characterization of the luminal cell hierarchy of the mammary gland
Mona Shehata, Andrew Teschendorff, Gemma Sharp, Nikola Novcic, Alasdair Russell, Stefanie Avril, Michael Prater, Peter Eirew, Carlos Caldas, Christine J Watson and John Stingl
Introduction The organization of the mammary epithelial hierarchy is poorly understood. It is our hypothesis that the luminal cell compartment is more complex than initially described, and that an understanding of the developmental relationships within this lineage will help in understanding the cellular context in which breast tumours occur. Methods We used fluorescence-activated cell sorting along with in vitro and in vivo functional assays to examine the growth and differentiation properties of distinct subsets of human and mouse mammary epithelial cells. We also examined how loss of steroid hormones influenced these populations in vivo. Gene expression profiles were also obtained for all the purified cell populations and correlated to those obtained from breast tumours. Results The luminal cell compartment of the mouse mammary gland can be resolved into non-clonogenic oestrogen receptor (ER+) luminal cells, ER+ luminal progenitors and ER- luminal progenitors. The ER+ luminal progenitors are unique in regards to cell survival, as they are relatively insensitive to loss of oestrogen and progesterone when compared to the other types of mammary epithelial cells. Analysis of normal human breast tissue reveals a similar hierarchical organization composed of non-clonogenic luminal cells, relatively differentiated (EpCAM+CD49f+ALDH-) and undifferentiated (EpCAM+CD49f+ALDH+) luminal progenitors. In addition, approximately one quarter of human breast samples examined contained an additional population that had a distinct luminal progenitor phenotype, characterized by low expression of ERBB3 and low proliferative potential. Parent-progeny relationship experiments demonstrated that all luminal progenitor populations in both species are highly plastic and, at low frequencies, can generate progeny representing all mammary cell types. The ER- luminal progenitors in the mouse and the ALDH+ luminal progenitors in the human appear to be analogous populations since they both have gene signatures that are associated with alveolar differentiation and resemble those obtained from basal-like breast tumours. Conclusions The luminal cell compartment in the mammary epithelium is more heterogeneous than initially perceived since progenitors of varying levels of luminal cell differentiation and proliferative capacities can be identified. An understanding of these cells will be essential for understanding the origins and the cellular context of human breast tumours
