Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma.
Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma.
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DOI：
10.1016/j.matbio.2011.09.001
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发表时间：
2012-01
期刊：
影响因子：
6.9
通讯作者：
Segars, James H.
中科院分区：
文献类型：
--
作者：
Norian, John M.;Owen, Carter M.;Taboas, Juan;Korecki, Casey;Tuan, Rocky;Malik, Minnie;Catherino, William H.;Segars, James H.
关键词：
平滑肌瘤是子宫内常见的肿瘤，其特征是坚硬、无序的细胞外基质（ECM）过度沉积。机械应力是过度ECM沉积的关键决定因素，并且已显示增加的机械应力参与肿瘤发生。在这里，我们测试了平滑肌瘤的粘弹性，并采用三种方法，包括测量活性RhoA，在平滑肌瘤细胞的动态和静态机械信号的特点。我们发现，峰值应变和假动态模量的平滑肌瘤组织显着增加，相对于匹配的子宫肌层。此外，平滑肌瘤细胞表现出衰减的反应所施加的周期性单轴应变和基板刚度的变化，相对于子宫肌层细胞。然而，在一个灵活的pronectin涂层硅基板，基础水平和溶血磷脂酸刺激水平的激活RhoA之间的平滑肌瘤和子宫肌层细胞相似。相比之下，与子宫肌层细胞相比，铺在刚性聚苯乙烯基底上的平滑肌瘤细胞具有升高的活性RhoA水平。结果表明，平滑肌瘤的ECM的粘弹性有助于显着的肿瘤的固有刚度和平滑肌瘤细胞具有衰减的敏感性机械线索。研究结果表明，在平滑肌瘤细胞中，外部机械环境（细胞外力）和RhoA介导的肌动蛋白细胞骨架重组之间的通信可能存在根本性的改变。需要进一步的研究来阐明子宫肌瘤细胞中机械信号减弱的机制。
Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA. We found that the peak strain and pseudo-dynamic modulus of leiomyoma tissue was significantly increased relative to matched myometrium. In addition, leiomyoma cells demonstrated an attenuated response to applied cyclic uniaxial strain and to variation in substrate stiffness, relative to myometrial cells. However, on a flexible pronectin-coated silicone substrate, basal levels and lysophosphatidic acid-stimulated levels of activated RhoA were similar between leiomyoma and myometrial cells. In contrast, leiomyoma cells plated on a rigid polystyrene substrate had elevated levels of active RhoA, compared to myometrial cells. The results indicate that viscoelastic properties of the ECM of leiomyoma contribute significantly to the tumor’s inherent stiffness and that leiomyoma cells have an attenuated sensitivity to mechanical cues. The findings suggest there may be a fundamental alteration in the communication between the external mechanical environment (extracellular forces) and reorganization of the actin cytoskeleton mediated by RhoA in leiomyoma cells. Additional research will be needed to elucidate the mechanism(s) responsible for the attenuated mechanical signaling in leiomyoma cells.
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影响因子：
7.5
作者：
Chicurel, ME;Chen, CS;Ingber, DE
通讯作者：
Ingber, DE
DOI：
10.1126/stke.2002.119.pe6
发表时间：
2002-02-12
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Alenghat, Francis J;Ingber, Donald E
通讯作者：
Ingber, Donald E
DOI：
10.1073/pnas.0800835105
发表时间：
2008-08-12
影响因子：
11.1
作者：
Ghosh, Kaustabh;Thodeti, Charles K.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
3.4
作者：
Engler, A;Bacakova, L;Discher, D
通讯作者：
Discher, D