• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>PLoS Computational Biology >Evolution and Phenotypic Selection of Cancer Stem Cells
【24h】

Evolution and Phenotypic Selection of Cancer Stem Cells

机译：癌症干细胞的进化和表型选择

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cells of different organs at different ages have an intrinsic set of kinetics that dictates their behavior. Transformation into cancer cells will inherit these kinetics that determine initial cell and tumor population progression dynamics. Subject to genetic mutation and epigenetic alterations, cancer cell kinetics can change, and favorable alterations that increase cellular fitness will manifest themselves and accelerate tumor progression. We set out to investigate the emerging intratumoral heterogeneity and to determine the evolutionary trajectories of the combination of cell-intrinsic kinetics that yield aggressive tumor growth. We develop a cellular automaton model that tracks the temporal evolution of the malignant subpopulation of so-called cancer stem cells(CSC), as these cells are exclusively able to initiate and sustain tumors. We explore orthogonal cell traits, including cell migration to facilitate invasion, spontaneous cell death due to genetic drift after accumulation of irreversible deleterious mutations, symmetric cancer stem cell division that increases the cancer stem cell pool, and telomere length and erosion as a mitotic counter for inherited non-stem cancer cell proliferation potential. Our study suggests that cell proliferation potential is the strongest modulator of tumor growth. Early increase in proliferation potential yields larger populations of non-stem cancer cells(CC) that compete with CSC and thus inhibit CSC division while a reduction in proliferation potential loosens such inhibition and facilitates frequent CSC division. The sub-population of cancer stem cells in itself becomes highly heterogeneous dictating population level dynamics that vary from long-term dormancy to aggressive progression. Our study suggests that the clonal diversity that is captured in single tumor biopsy samples represents only a small proportion of the total number of phenotypes.
机译：不同年龄的不同器官的细胞有一个内在的动力学，决定了他们的行为。转化为癌细胞将继承这些动力学，该动力学确定初始细胞和肿瘤群体进展动态。受到遗传突变和表观遗传的改变，癌细胞动力学可以改变，增加细胞健身的有利改变将显示出来并加速肿瘤进展。我们开始研究新兴的肿瘤内异质性，并确定细胞内在动力学组合的进化轨迹，从而产生积极的肿瘤生长。我们开发一种蜂窝自动机型模型，追踪所谓的癌症干细胞（CSC）的恶性群的时间演变，因为这些细胞专门能够引发和维持肿瘤。我们探索正交细胞性状，包括细胞迁移，以促进侵袭，由于遗传漂移，由于累积不可逆的有害突变，对称癌症干细胞分裂增加癌症干细胞，以及作为有丝分裂柜台的端粒长度和侵蚀遗传的非茎癌细胞增殖潜力。我们的研究表明，细胞增殖潜力是肿瘤生长的最强调节剂。增殖潜力的早期增加产生了与CSC竞争的非茎癌细胞（CC）的较大群体，从而抑制CSC划分，同时降低增殖潜力损伤这种抑制并促进频繁的CSC分裂。癌症干细胞本身的亚群成为高度异质的列长群体水平动态，其因长期休眠而与侵略性的进展不同。我们的研究表明，单一肿瘤活检样本中捕获的克隆多样性仅占表型总数的小比例。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号