2012年10月30日 訊 /生物谷BIOON/ --在以前的研究中,，科學(xué)家們只知道乳腺中的一種類型的祖細(xì)胞。在一項新的研究中,，來自英國癌癥研究院劍橋研究所的研究人員在乳腺中鑒定出至少兩類被稱作祖細(xì)胞的早期細(xì)胞,。不同于干細(xì)胞：它能夠分化為任何類型的細(xì)胞并且持續(xù)進(jìn)行細(xì)胞分裂，祖細(xì)胞只能夠進(jìn)行有限次細(xì)胞分裂,。不同的祖細(xì)胞可能解釋著為何存在著不同類型的乳腺癌,。這項新的研究發(fā)現(xiàn)揭示出不同乳腺癌起源的線索，并且為有助于開發(fā)出潛在的新藥物靶標(biāo),。相關(guān)研究結(jié)果刊登在Breast Cancer Research期刊上,。
研究人員發(fā)現(xiàn)一類被稱作雌激素陽性祖細(xì)胞(oestrogen positive progenitor)的祖細(xì)胞含有雌激素受體。這種受體蛋白接受來自雌激素的信號,。另一類被稱作雌激素陰性祖細(xì)胞的祖細(xì)胞缺乏這種受體,。
雌激素陽性祖細(xì)胞在低水平雌激素和黃體酮的環(huán)境---如絕經(jīng)后女性的乳腺組織---中更好地存活下來。這提示著絕經(jīng)后女性所患的乳腺瘤可能是由這類祖細(xì)胞產(chǎn)生的,，不過還需開展進(jìn)一步的研究來證實這一點,。
雌激素陰性祖細(xì)胞的遺傳指紋(genetic fingerprint)類似于一種侵襲性的乳腺癌，即基底樣乳腺癌(basal-like breast cancer),，因此這類祖細(xì)胞更可能影響較為年輕的女性,。這提示著這種乳腺癌可能是由這類雌激素陰性祖細(xì)胞產(chǎn)生的。
論文通信作者John Stingl說,，“這種激動人心的發(fā)現(xiàn)揭示出乳腺要比科學(xué)家們起初所認(rèn)為的更加復(fù)雜,。發(fā)現(xiàn)新類型的祖細(xì)胞可能解釋著為何存在不同類型的乳腺癌，以及為何年輕和年老的女性往往患上不同類型的乳腺癌,。在未來,，它也可能提供新的起點來診斷和治療這種疾病。”(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
