Cellular quiescence in mammary stem cells and breast tumor stem cells: got testable hypotheses?
Cellular quiescence in mammary stem cells and breast tumor stem cells: got testable hypotheses?
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DOI：
10.1007/s10911-009-9111-2
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发表时间：
2009-03
影响因子：
2.5
通讯作者：
DiRenzo, James
中科院分区：
文献类型：
--
作者：
Harmes, David C.;DiRenzo, James
细胞静止是一种可逆性的细胞周期停滞状态，最近被证明是对分化的阻碍，并与对癌症化疗药物和其他外源药物的耐药性有关；这些特征在成人干细胞和可能的肿瘤干细胞中是常见的。乳腺再生的双相动力学，再加上其循环的内分泌控制，表明乳腺干细胞很可能在再生周期的一个狭窄窗口内分裂，并返回到静止状态。这将使它们能够保持其增殖能力，抵抗分化信号，并保持其延长的寿命。越来越多的证据表明，乳腺干细胞和其他成人干细胞利用静止来达到这一目的，然而，肿瘤干细胞在多大程度上做到了这一点还不清楚。乳腺干细胞保留的增殖能力可能使它们能够积累和藏匿导致乳腺癌发生的突变。然而，目前尚不清楚这些致病病变是否会导致乳腺干细胞的缺陷或错乱的静止。这种效应的证据可能会导致监测乳腺干细胞静止或激活的诊断系统的开发。这样的系统可能会对有重大乳腺癌风险的患者进行评估。此外，静止期被认为与治疗抵抗和肿瘤复发有关。本综述旨在评价目前已知的调控细胞静止的机制，以及肿瘤干细胞静止在乳腺癌复发中的作用。
Cellular quiescence is a state of reversible cell cycle arrest and has more recently been shown to be a blockade to differentiation and to correlate with resistance to cancer chemotherapeutics and other xenobiotics; features that are common to adult stem cells and possibly tumor stem cells. The biphasic kinetics of mammary regeneration, coupled to its cyclic endocrine control suggest that mammary stem cells most likely divide during a narrow window of the regenerative cycle and return to a state of quiescence. This would enable them to retain their proliferative capacity, resist differentiation signals and preserve their prolonged life span. There is accumulating evidence that mammary stem cells and other adult stem cells utilize quiescence for this purpose, however the degree to which tumor stem cells do so is largely unknown. The retained proliferative capacity of mammary stem cells likely enables them to accumulate and harbor mutations that lead to breast cancer initiation. However it is currently unclear if these causative lesions lead to defective or deranged quiescence in mammary stem cells. Evidence of such effects could potentially lead to the development of diagnostic systems that monitor mammary stem cell quiescence or activation. Such systems may be useful for the evaluation of patients who are at significant risk of breast cancer. Additionally quiescence has been postulated to contribute to therapeutic resistance and tumor recurrence. This review aims to evaluate what is known about the mechanisms governing cellular quiescence and the role of tumor stem cell quiescence in breast cancer recurrence.
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