Soft Substrates Containing Hyaluronan Mimic the Effects of Increased Stiffness on Morphology, Motility, and Proliferation of Glioma Cells.
Soft Substrates Containing Hyaluronan Mimic the Effects of Increased Stiffness on Morphology, Motility, and Proliferation of Glioma Cells.
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DOI：
10.1021/acs.biomac.7b00324
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发表时间：
2017-10-09
影响因子：
6.2
通讯作者：
Janmey PA
中科院分区：
文献类型：
--
作者：
Pogoda K;Bucki R;Byfield FJ;Cruz K;Lee T;Marcinkiewicz C;Janmey PA
与许多其他癌细胞生长在以异常坚硬的富含胶原的基质为特征的肿瘤中不同，胶质瘤细胞在更柔软的大脑环境中增殖和迁移，这种环境通常缺乏乳腺癌、肝癌、结肠直肠癌和其他类型癌症所特有的丝状蛋白基质。神经胶质细胞衍生的肿瘤及其衍生的细胞在其机械特性、对治疗的反应和体外特性方面具有高度异质性和可变性。在离体测量时，一些胶质瘤样品比正常大脑更硬，但即使是那些在体外柔软的胶质瘤样品，在体内肿瘤环境中产生的压力梯度变形后也会变硬。这种机械差异可以强烈地改变培养的胶质瘤细胞的表型。或者，化学信号可能会通过激活细胞内的信使来引起与初始刺激相同的增加僵硬的表型。在这项研究中，比较了三种不同的人类胶质瘤细胞系对底物硬度变化的反应，以及它们在由透明质酸和特定整合素配体（层粘连蛋白或胶原i）组合组成的非常软底物上的反应。通过定量细胞形态、硬度、活力、增殖和细胞因子IL-8的分泌，胶质瘤细胞对增加的硬度的反应显示几乎相同的底物引起含有透明质酸，即使在没有增加的硬度。对透明质酸的反应需要pi3激酶活性，而对硬度的反应不需要。这一结果表明透明质酸可以触发相同的细胞反应，就像从僵硬的环境中获得的机械力一样，并表明肿瘤微环境的化学和机械特征可以在癌细胞中实现等效的反应。
Unlike many other cancer cells that grow in tumors characterized by an abnormally stiff collagen-enriched stroma, glioma cells proliferate and migrate in the much softer environment of the brain, which generally lacks the filamentous protein matrix characteristic of breast, liver, colorectal, and other types of cancer. Glial cell-derived tumors and the cells derived from them are highly heterogeneous and variable in their mechanical properties, their response to treatments, and their properties in vitro. Some glioma samples are stiffer than normal brain when measured ex vivo, but even those that are soft in vitro stiffen after deformation by pressure gradients that arise in the tumor environment in vivo. Such mechanical differences can strongly alter the phenotype of cultured glioma cells. Alternatively, chemical signaling might elicit the same phenotype as increased stiffness by activating intracellular messengers common to both initial stimuli. In this study the responses of three different human glioma cell lines to changes in substrate stiffness are compared with their responses on very soft substrates composed of a combination of hyaluronic acid and a specific integrin ligand, either laminin or collagen I. By quantifying cell morphology, stiffness, motility, proliferation, and secretion of the cytokine IL-8, glioma cell responses to increased stiffness are shown to be nearly identically elicited by substrates containing hyaluronic acid, even in the absence of increased stiffness. PI3-kinase activity was required for the response to hyaluronan but not to stiffness. This outcome suggests that hyaluronic acid can trigger the same cellular response, as can be obtained by mechanical force transduced from a stiff environment, and demonstrates that chemical and mechanical features of the tumor microenvironment can achieve equivalent reactions in cancer cells.
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DOI：
10.1158/1541-7786.mcr-13-0629
发表时间：
2014-10
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Kim Y;Kumar S
通讯作者：
Kumar S
影响因子：
7.8
作者：
Kozlov, Michael M;Bershadsky, Alexander D
通讯作者：
Bershadsky, Alexander D
影响因子：
--
作者：
Lin HH;Lin HK;Lin IH;Chiou YW;Chen HW;Liu CY;Harn HI;Chiu WT;Wang YK;Shen MR;Tang MJ
通讯作者：
Tang MJ
影响因子：
16.6
作者：
Bangasser BL;Shamsan GA;Chan CE;Opoku KN;Tüzel E;Schlichtmann BW;Kasim JA;Fuller BJ;McCullough BR;Rosenfeld SS;Odde DJ
通讯作者：
Odde DJ
放射治疗后小鼠脑肿瘤的纵向磁共振弹性成像研究
影响因子：
3.5
作者：
Feng Y;Clayton EH;Okamoto RJ;Engelbach J;Bayly PV;Garbow JR
通讯作者：
Garbow JR