Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences- Oncology Center, and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Lab Chip. 2012 Nov 7;12(21):4244-8. doi: 10.1039/c2lc40819h.
The extracellular matrix (ECM) of the tumor niche provides support to residing and migrating cells and presents instructive cues that influence cellular behaviours. The ECM protein fibronectin (Fn) enables vascular network formation, while hyaluronic acid (HA) is known to facilitate breast tumor development. To recapitulate aspects of the tumor microenvironment, we developed systems of spatially defined Fn and HA for the co-culture of endothelial colony forming cells (ECFCs) and breast cancer cells (BCCs). A micropatterned system was developed using sequential microcontact printing of HA and Fn. This approach supported the preferential adhesion of ECFCs to Fn, but did not support the preferential adhesion of BCCs to HA. Thus, we developed a microstructured analog to spatially organize BCC-laden HA micromolded hydrogels adjacent to ECFCs in fibrin hydrogels. These novel, miniaturized systems allow the analysis of the spatial and temporal mechanisms regulating tumor angiogenesis, and can be applied to mimic other microenvironments of healthy and diseased tissues.
肿瘤微环境中的细胞外基质（ECM）为定居和迁移细胞提供支持，并提供影响细胞行为的指导线索。ECM 蛋白纤维连接蛋白（Fn）能够促进血管网络的形成，而透明质酸（HA）则有助于乳腺癌的发展。为了再现肿瘤微环境的某些方面，我们开发了空间限定的 Fn 和 HA 系统，用于内皮集落形成细胞（ECFCs）和乳腺癌细胞（BCCs）的共培养。通过 HA 和 Fn 的顺序微接触印刷开发了一种微图案系统。这种方法支持 ECFC 优先黏附到 Fn，但不支持 BCC 优先黏附到 HA。因此，我们开发了一种微结构模拟物，用于将富含 BCC 的 HA 微成型水凝胶在纤维蛋白水凝胶中与 ECFC 相邻进行空间组织。这些新颖的小型化系统允许分析调节肿瘤血管生成的时空机制，并且可以应用于模拟健康和患病组织的其他微环境。
