Microenvironment complexity and matrix stiffness regulate breast cancer cell activity in a 3D in vitro model.
Microenvironment complexity and matrix stiffness regulate breast cancer cell activity in a 3D in vitro model.
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DOI：
10.1038/srep35367
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发表时间：
2016-10-13
影响因子：
4.6
通讯作者：
Scaglione S
中科院分区：
文献类型：
--
作者：
Cavo M;Fato M;Peñuela L;Beltrame F;Raiteri R;Scaglione S
三维(3D)细胞培养是理解正常和病理条件下细胞现象的基本工具。特别是，机械和化学刺激在细胞命运、癌症的发生和恶性演变中发挥着相关的作用。在这里，我们使用机械调节的藻酸盐水凝胶来研究底物弹性对乳腺腺癌细胞活性的影响。用原子力显微镜测量了水凝胶的弹性模量，得到了一个显著的范围(15 0~4 0 0 0 kpa)。将乳腺癌细胞株MCF-7种植在3D凝胶中，接种在标准的培养皿和海藻酸盐包被的培养皿中(2D对照)。细胞在3D和2D培养时表现出显著的形态差异，在两种2D条件下都表现出扁平的形状，同时在凝胶中保持圆形、椭圆形组织(簇)构象，类似于体内的构象。此外，我们观察到细胞活力和底物弹性之间存在严格的相关性；尤其是，随着水凝胶弹性的增加，MCF-7细胞的数量不断减少。值得注意的是，与细胞团形成相关的最高细胞增殖率仅在最软的水凝胶(E = 150-200 kpa)中出现在两周内，这突显了采用更现实和先验定义的模型进行体外癌症研究的必要性。
Three-dimensional (3D) cell cultures represent fundamental tools for the comprehension of cellular phenomena both in normal and in pathological conditions. In particular, mechanical and chemical stimuli play a relevant role on cell fate, cancer onset and malignant evolution. Here, we use mechanically-tuned alginate hydrogels to study the role of substrate elasticity on breast adenocarcinoma cell activity. The hydrogel elastic modulus (E) was measured via atomic force microscopy (AFM) and a remarkable range (150–4000 kPa) was obtained. A breast cancer cell line, MCF-7, was seeded within the 3D gels, on standard Petri and alginate-coated dishes (2D controls). Cells showed dramatic morphological differences when cultured in 3D versus 2D, exhibiting a flat shape in both 2D conditions, while maintaining a circular, spheroid-organized (cluster) conformation within the gels, similar to those in vivo. Moreover, we observed a strict correlation between cell viability and substrate elasticity; in particular, the number of MCF-7 cells decreased constantly with increasing hydrogel elasticity. Remarkably, the highest cellular proliferation rate, associated with the formation of cell clusters, occurred at two weeks only in the softest hydrogels (E = 150–200 kPa), highlighting the need to adopt more realistic and a priori defined models for in vitro cancer studies.
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影响因子：
3.8
作者：
Discher, Dennis;Dong, Cheng;Fredberg, Jeffrey J.;Guilak, Farshid;Ingber, Donald;Janmey, Paul;Kamm, Roger D.;Schmid-Schoenbein, Geert W.;Weinbaum, Sheldon
通讯作者：
Weinbaum, Sheldon
影响因子：
19
作者：
Agarwal A;Farouz Y;Nesmith AP;Deravi LF;McCain ML;Parker KK
通讯作者：
Parker KK
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
14
作者：
Awad, HA;Wickham, MQ;Guilak, F
通讯作者：
Guilak, F
影响因子：
3.4
作者：
Engler, A;Bacakova, L;Discher, D
通讯作者：
Discher, D