Zebrafish as a Model for Cancer Self-Renewal
Zebrafish as a Model for Cancer Self-Renewal
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DOI：
10.1089/zeb.2009.0610
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发表时间：
2009-12-01
期刊：
影响因子：
2
通讯作者：
Langenau, David M.
中科院分区：
文献类型：
--
作者：
Ignatius, Myron S.;Langenau, David M.
自我更新是正常干细胞和癌细胞自我更新的过程。在癌症中，这一过程最终导致了恶性细胞的无限复制潜力，并且很可能在逃避常规治疗的残留细胞群中发现。已经出现了两种本质上相反的假设来解释癌症中的自我更新是如何发生的。癌症干细胞假说指出，自我更新仅限于恶性细胞的离散亚群，而随机模型表明所有肿瘤细胞都具有自我更新的潜力。目前，测量癌症自我更新的黄金标准是将有限稀释细胞移植到免疫匹配或免疫缺陷的动物中。从这些实验中，可以根据移植不同剂量的肿瘤细胞后携带疾病的动物数量来计算肿瘤起始频率。在这里，我们描述了如何进行自我更新测定，总结了当前支持癌症干细胞的实验模型和癌症自我更新的随机模型，并列举了如何利用斑马鱼来揭示癌症自我更新的重要途径。
Self-renewal is the process by which normal stem cells and cancer cells make more of themselves. In cancer, this process is ultimately responsible for the infinite replicative potential of malignant cells and is likely found in residual cell populations that evade conventional therapy. Two intrinsically opposing hypotheses have emerged to explain how self-renewal occurs in cancer. The cancer stem cell hypothesis states that self-renewal is confined to a discrete subpopulation of malignant cells, whereas the stochastic model suggests that all tumor cells have the potential to self-renew. Presently, the gold standard for measuring cancer self-renewal is limiting dilution cell transplantation into immune-matched or immune-deficient animals. From these experiments, tumor-initiating frequency can be calculated based on the number of animals that engraft disease following transplantation of various doses of tumor cells. Here, we describe how self-renewal assays are performed, summarize the current experimental models that support the cancer stem cell and stochastic models of cancer self-renewal, and enumerate how the zebrafish can be used to uncover important pathways in cancer self-renewal.