Cytostasis and morphological changes induced by mifepristone in human metastatic cancer cells involve cytoskeletal filamentous actin reorganization and impairment of cell adhesion dynamics.
Cytostasis and morphological changes induced by mifepristone in human metastatic cancer cells involve cytoskeletal filamentous actin reorganization and impairment of cell adhesion dynamics.
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DOI：
10.1186/1471-2407-13-35
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发表时间：
2013-01-26
期刊：
影响因子：
3.8
通讯作者：
Telleria CM
中科院分区：
文献类型：
--
作者：
Brandhagen BN;Tieszen CR;Ulmer TM;Tracy MS;Goyeneche AA;Telleria CM
细胞骨架动力学中的细胞形状和可塑性的变化与细胞粘附、迁移、侵袭和转移的整个过程密切相关。我们实验室以前的工作表明，合成类固醇米非司酮抑制高转移性癌细胞的生长，同时引起细胞形态的显着变化。在这里，我们评估了这种形态学的改变是否在响应米非司酮的细胞生长抑制浓度是可逆的或永久的，涉及重排的细胞骨架蛋白，和/或影响粘附能力的细胞。卵巢癌细胞系（SKOV-3），乳腺癌细胞系（MDA-MB-231），前列腺癌细胞系（LNCaP）和神经系统癌细胞系（U87 MG）暴露于细胞生长抑制浓度的米非司酮中，并通过相差显微镜进行研究。米非司酮引起的细胞停滞和形态学变化的暂时性或永久性的性质进行了评估，以及细胞骨架蛋白的重排。使用去粘附和粘附测定来确定当与媒介物处理的对照相比时，米非司酮阻滞和形态失调的细胞是否具有异常的去粘附/粘附动力学。米非司酮处理的细胞显示长，薄，梭形的形状与边界类似的松散粘附的细胞。米非司酮引起的生长停滞和形态学变化在SKOV-3、MDA-MB-231和U87 MG中是可逆的，但在LNCaP细胞中不是，而是变得衰老。所有的癌细胞类型暴露于米非司酮显示大大增加肌动蛋白皱褶与加速脱粘从培养板，并延迟粘附能力的各种细胞外基质成分。米非司酮的细胞抑制浓度诱导了一组不同来源组织的侵袭性、高转移性癌细胞的细胞结构改变。这种变化与肌动蛋白纤维的重新分布有关，肌动蛋白纤维主要形成非粘附性膜皱褶，导致细胞粘附能力失调。
Changes in cell shape and plasticity in cytoskeletal dynamics are critically involved in cell adhesion, migration, invasion and the overall process of metastasis. Previous work in our laboratory demonstrated that the synthetic steroid mifepristone inhibited the growth of highly metastatic cancer cells, while simultaneously causing striking changes in cellular morphology. Here we assessed whether such morphological alterations developed in response to cytostatic concentrations of mifepristone are reversible or permanent, involve rearrangement of cytoskeletal proteins, and/or affect the adhesive capacity of the cells. Cancer cell lines of the ovary (SKOV-3), breast (MDA-MB-231), prostate (LNCaP), and nervous system (U87MG) were exposed to cytostatic concentrations of mifepristone and studied by phase-contrast microscopy. The transient or permanent nature of the cytostasis and morphological changes caused by mifepristone was assessed, as well as the rearrangement of cytoskeletal proteins. De-adhesion and adhesion assays were utilized to determine if mifepristone-arrested and morphologically dysregulated cells had abnormal de-adhesion/adhesion dynamics when compared to vehicle-treated controls. Mifepristone-treated cells displayed a long, thin, spindle-like shape with boundaries resembling those of loosely adhered cells. Growth arrest and morphology changes caused by mifepristone were reversible in SKOV-3, MDA-MB-231 and U87MG, but not in LNCaP cells that instead became senescent. All cancer cell types exposed to mifepristone displayed greatly increased actin ruffling in association with accelerated de-adhesion from the culture plate, and delayed adhesion capacity to various extracellular matrix components. Cytostatic concentrations of mifepristone induced alterations in the cellular structure of a panel of aggressive, highly metastatic cancer cells of different tissues of origin. Such changes were associated with re-distribution of actin fibers that mainly form non-adhesive membrane ruffles, leading to dysregulated cellular adhesion capacity.