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首页> 外文学位 >Breast tumor stem cells have increased microtentacles that can be targeted therapeutically with curcumin.
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Breast tumor stem cells have increased microtentacles that can be targeted therapeutically with curcumin.

机译：乳腺癌干细胞的微触角增加，可以用姜黄素治疗。

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摘要

Cancer stem-like cells (CSC) and circulating tumor cells (CTCs) have related properties associated with distant metastasis, but the mechanisms through which CSCs promote metastasis are unclear. In this study, we report that breast cancer cell lines with more stem-like properties display higher levels of microtentacles (McTNs), a type of tubulin-based protrusion of the plasma cell membrane which forms on detached or suspended cells and aid in cell reattachment. We hypothesized that CSCs with large numbers of McTNs would more efficiently attach to distant tissues, promoting metastatic efficiency. The naturally occurring stem-like subpopulation of the HMLE breast cell line presents increased McTNs compared to its isogenic non-stem-like subpopulation, when these subpopulations are separated by flow cytometry. This increase in McTNs was supported by elevated &agr;-tubulin detyrosination and vimentin protein levels and organization. Increased McTNs in stem-like HMLEs promoted a faster initial reattachment of suspended cells that was inhibited by the tubulin-directed drug, colchicine, confirming a functional role for McTNs in stem cell reattachment. Moreover, live cell confocal microscopy showed that McTNs persist in breast stem cell mammospheres as flexible, motile protrusions on the surface of the mammosphere. While exposed to the environment, they also function as extensions between adjacent cells along cell-cell junctions. We found that treatment with the breast CSC-targeting compound curcumin rapidly extinguished McTNs in breast CSCs, preventing reattachment from suspension. Together, our results support a model in which breast CSCs with cytoskeletal alterations that promote McTNs can mediate attachment and metastasis but might be targeted by curcumin as an anti-metastatic strategy.
机译：癌干样细胞（CSC）和循环肿瘤细胞（CTC）具有与远处转移相关的相关属性，但尚不清楚CSC促进转移的机制。在这项研究中，我们报告具有更多干样性质的乳腺癌细胞系显示出更高水平的微触角（McTNs），这是一种基于微管蛋白的浆细胞膜突起，形成于分离或悬浮的细胞上，并有助于细胞重新附着。我们假设具有大量McTN的CSC可以更有效地附着在远处的组织上，从而提高转移效率。 HMLE乳腺细胞系的天然干状亚群与其等基因非干状亚群相比，通过流式细胞仪分离时，其McTNs增加。 McTNs的这种增加由α-微管蛋白脱酪氨酸和波形蛋白蛋白水平和组织的升高所支持。干状HMLE中增加的McTNs促进了悬浮细胞的初始重新附着更快，这被微管蛋白定向药物秋水仙碱抑制，证实了McTNs在干细胞重新附着中的功能作用。此外，活细胞共聚焦显微镜显示，McTNs在乳房干细胞乳腺球中持续存在，是乳腺球表面上的柔性，活动性突起。当暴露于环境中时，它们还充当相邻细胞之间沿细胞间连接的延伸。我们发现，以乳腺靶向CSC的复合姜黄素治疗可快速消除乳腺CSC中的McTN，从而避免了从悬吊中重新附着。在一起，我们的结果支持一个模型，在该模型中，具有促进McTNs的细胞骨架改变的乳腺CSC可以介导附着和转移，但姜黄素可能将其作为抗转移策略。

著录项

  • 作者

    Charpentier, Monica Simone.;

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Biology Cell.;Health Sciences Oncology.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 125 p.
  • 总页数 125
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

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