Hybrid collagen alginate hydrogel as a platform for 3D tumor spheroid invasion.
Hybrid collagen alginate hydrogel as a platform for 3D tumor spheroid invasion.
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DOI：
10.1016/j.actbio.2018.06.003
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发表时间：
2018-07-15
影响因子：
9.7
通讯作者：
Luker GD
中科院分区：
文献类型：
--
作者：
Liu C;Lewin Mejia D;Chiang B;Luker KE;Luker GD
细胞外基质通过生物化学和机械信号调节癌症的标志性特征，尽管由于缺乏重建肿瘤生理学的模型，对这些过程的机械理解仍然受到限制。为了重现肿瘤中的三维结构和信号传导的组织工程模型，迫切需要允许灵活控制机械和生物物理特征的新材料。我们开发了一种由胶原蛋白和藻酸盐组成的混合水凝胶系统，用于模拟乳腺癌和其他恶性肿瘤的肿瘤环境。水凝胶的材料性质，包括刚度、微观结构和孔隙率，包括正常器官和肿瘤中存在的参数。该水凝胶具有良好的组织，均匀的微观结构，具有可调节的机械刚度和优异的渗透性。在包埋多细胞肿瘤球体后，我们构建了一个3D肿瘤侵袭模型，该模型显示了与体内相似的跟随前导迁移的成纤维细胞导致癌细胞的侵袭。我们还证明了CXCL 12-CXCR 4信号传导的作用，这是一种与肿瘤进展和转移有关的途径，在3D水凝胶中的双肿瘤球体侵袭模型中。这些研究建立了一种新的水凝胶平台，其材料特性可以调整以研究环境条件对肿瘤进展的影响，这将推动未来对癌细胞侵袭和治疗反应的研究。
Extracellular matrix regulates hallmark features of cancer through biochemical and mechanical signals, although mechanistic understanding of these processes remains limited by lack of models that recreate physiology of tumors. To tissue-engineer models that recapitulate three-dimensional architecture and signaling in tumors, there is a pressing need for new materials permitting flexible control of mechanical and biophysical features. We developed a hybrid hydrogel system composed of collagen and alginate to model tumor environments in breast cancer and other malignancies. Material properties of the hydrogel, including stiffness, microstructure and porosimetry, encompass parameters present in normal organs and tumors. The hydrogel possesses a well-organized, homogenous microstructure with adjustable mechanical stiffness and excellent permeability. Upon embedding multicellular tumor spheroids, we constructed a 3D tumor invasion model showing follow-the-leader migration with fibroblasts leading invasion of cancer cells similar to in vivo. We also demonstrated effects of CXCL12-CXCR4 signaling, a pathway implicated in tumor progression and metastasis, in a dual-tumor spheroid invasion model in 3D hydrogels. These studies establish a new hydrogel platform with material properties that can be tuned to investigate effects of environmental conditions on tumor progression, which will advance future studies of cancer cell invasion and response to therapy.
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影响因子：
3.7
作者：
Gkretsi V;Stylianou A;Stylianopoulos T
通讯作者：
Stylianopoulos T
DOI：
10.1039/c4ib00015c
发表时间：
2014-05
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Cavnar SP;Ray P;Moudgil P;Chang SL;Luker KE;Linderman JJ;Takayama S;Luker GD
通讯作者：
Luker GD
DOI：
10.1126/science.1176009
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hynes RO
通讯作者：
Hynes RO
影响因子：
4.3
作者：
Cox TR;Erler JT
通讯作者：
Erler JT
影响因子：
48
作者：
Fischbach, Claudia;Chen, Ruth;Mooney, David J.
通讯作者：
Mooney, David J.