Smith Gilbert H, Boulanger Corinne A
Mammary Biology Group, Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892, USA.
Mech Ageing Dev. 2002 Sep;123(11):1505-19. doi: 10.1016/s0047-6374(02)00114-8.
The proliferative lifespan of mammary stem cells was examined in serially transplanted clonal-dominant epithelial populations. Five successive transplant generations were done. The epithelial cell number in each outgrowth expands approximately 500-fold in nulliparous hosts and approximately 10000-fold in impregnated hosts. Despite this, all resulting mammary outgrowths showed lineal identity with the original. Growth senescence was observed in some implants beginning at the third generation in impregnated recipients. The ability of an individual implant to support ductal morphogenesis and also secretory lobule development decayed at independent rates. Individual implants from a single clonal-dominant outgrowth occasionally gave rise to markedly different ductal development within the same host indicating an epithelial cell autonomous mechanism in ductal patterning. Both premalignant and malignant populations appeared focally within the aging transplants. These populations were also lineally related to the original outgrowth supporting the conclusion that the primary growth was derived clonally from one or a few lineally related antecedents. The premalignant and malignant descendant populations no longer exhibit growth senescence suggesting that they are supported by a perpetually self-renewing progenitor. Our evidence indicates that a single mammary cell may have the capacity to self-renew through five transplant generations. Even some sixth generation implants show vigorous growth.
在连续移植的克隆主导上皮群体中检测了乳腺干细胞的增殖寿命。进行了连续五代移植。在未生育的宿主中，每个增生中的上皮细胞数量大约扩增500倍，在怀孕的宿主中大约扩增10000倍。尽管如此，所有产生的乳腺增生都与原始增生表现出谱系一致性。在怀孕受体的一些移植中，从第三代开始观察到生长衰老。单个移植支持导管形态发生以及分泌小叶发育的能力以独立的速率衰退。来自单个克隆主导增生的单个移植偶尔会在同一宿主体内产生明显不同的导管发育，这表明导管形成中存在上皮细胞自主机制。癌前和恶性群体在衰老的移植中呈局灶性出现。这些群体也与原始增生存在谱系关系，支持了主要生长是克隆地来源于一个或几个谱系相关的前体细胞的结论。癌前和恶性后代群体不再表现出生长衰老，这表明它们由持续自我更新的祖细胞支持。我们的证据表明，单个乳腺细胞可能有能力通过五代移植进行自我更新。甚至一些第六代移植也显示出旺盛的生长。
