The independent roles of mechanical, structural and adhesion characteristics of 3D hydrogels on the regulation of cancer invasion and dissemination
The independent roles of mechanical, structural and adhesion characteristics of 3D hydrogels on the regulation of cancer invasion and dissemination
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DOI：
10.1016/j.biomaterials.2013.08.077
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发表时间：
2013-12-01
期刊：
影响因子：
14
通讯作者：
Ewald, Andrew J.
中科院分区：
文献类型：
--
作者：
Beck, Jennifer N.;Singh, Anirudha;Ewald, Andrew J.
转移开始于癌细胞从原发肿瘤中逃逸或扩散。我们最近证明，肿瘤优先扩散到胶原蛋白I，而不是基底膜蛋白凝胶（基质胶）。在这项研究中，我们使用合成聚合物系统来定义可能导致传播到Matrigel中的材料特性。我们首先通过改变Matrigel支架内聚乙二醇（PEG）网络的交联密度来具体改变刚性。增加微环境刚性限制上皮生长，但不促进传播。接下来，我们使用肽缀合的环糊精（α-CDYRGDS）环将粘附信号并入PEG网络中。α-CDYRGDS环沿着PEG聚合物穿过，使得能够独立控制基质力学、粘附肽组成和粘附密度。粘合剂PEG网络诱导正常和恶性乳腺上皮细胞在中间值的粘附和刚度的传播。我们的数据显示，微环境信号可以诱导正常和恶性上皮细胞的传播，而不需要胶原蛋白I的纤维结构或包含胶原蛋白I特异性粘附序列。最后，本研究中开发的纳米生物材料和测定方法通常可用于原代哺乳动物组织的3D培养，以及机械和粘附输入对3D肿瘤生长，侵袭和传播的特定作用的系统评价。(C)2013爱思唯尔有限公司保留所有权利。
Metastasis begins with the escape, or dissemination, of cancer cells from the primary tumor. We recently demonstrated that tumors preferentially disseminate into collagen I and not into basement membrane protein gels (Matrigel). In this study, we used synthetic polymer systems to define material properties that could induce dissemination into Matrigel. We first specifically varied rigidity by varying the crosslinking density of poly(ethylene glycol) (PEG) networks within Matrigel scaffolds. Increased microenvironmental rigidity limited epithelial growth but did not promote dissemination. We next incorporated adhesive signals into the PEG network using peptide-conjugated cyclodextrin (alpha-CDYRGDS) rings. The a-CDYRGDS rings threaded along the PEG polymers, enabling independent control of matrix mechanics, adhesive peptide composition, and adhesive density. Adhesive PEG networks induced dissemination of normal and malignant mammary epithelial cells at intermediate values of adhesion and rigidity. Our data reveal that microenvironmental signals can induce dissemination of normal and malignant epithelial cells without requiring the fibrillar structure of collagen I or containing collagen I-specific adhesion sequences. Finally, the nanobiomaterials and assays developed in this study are generally useful both in 3D culture of primary mammalian tissues and in the systematic evaluation of the specific role of mechanical and adhesive inputs on 3D tumor growth, invasion, and dissemination. (C) 2013 Elsevier Ltd. All rights reserved.