An Engineered Breast Cancer Model on a Chip to Replicate ECM‐Activation In Vitro during Tumor Progression,Advanced Healthcare Materials

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An Engineered Breast Cancer Model on a Chip to Replicate ECM‐Activation In Vitro during Tumor Progression
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2016-11-07 , DOI: 10.1002/adhm.201600772
Filomena Gioiella _{1,

2} , Francesco Urciuolo ₂ , Giorgia Imparato ₂ , Virginia Brancato ₁ , Paolo A. Netti _{1,

2,

3}

Affiliation

In this work, a new model of breast cancer is proposed featuring both epithelial and stromal tissues arranged on a microfluidic chip. The main task of the work is the in vitro replication of the stromal activation during tumor epithelial invasion. The activation of tumor stroma and its morphological/compositional changes play a key role in tumor progression. Despite emerging evidences, to date the activation of tumor stroma in vitro has not been achieved yet. The tumor‐on‐chip proposed in this work is built in order to replicate the features of its native counterpart: multicellularity (tumor epithelial cell and stromal cell); 3D engineered stroma compartment composed of cell‐assembled extracellular matrix (ECM); reliable 3D tumor architecture. During tumor epithelial invasion the stroma displayed an activation process at both cellular and ECM level. Similarly of what repeated in vivo, ECM remodeling is found in terms of hyaluronic acid and fibronectin overexpression in the stroma compartment. Furthermore, the cell‐assembled ECM featuring the stromal tissue, allowed on‐line monitoring of collagen remodeling during stroma activation process via real time multiphoton microscopy. Also, trafficking of macromolecules within the stromal compartment has been monitored in real time.

中文翻译：

芯片上设计的乳腺癌模型可在肿瘤进展过程中复制体外ECM激活

在这项工作中，提出了一种新的乳腺癌模型，其特征是上皮组织和基质组织都排列在微流控芯片上。这项工作的主要任务是在肿瘤上皮浸润过程中基质激活的体外复制。肿瘤基质的激活及其形态/组成变化在肿瘤进展中起关键作用。尽管有新的证据，但迄今为止尚未实现体外肿瘤基质的激活。这项工作中提出的芯片上肿瘤是为了复制其天然对应物的特征而构建的：多细胞性（肿瘤上皮细胞和基质细胞）；由细胞组装的细胞外基质（ECM）组成的3D工程基质室; 可靠的3D肿瘤架构。在肿瘤上皮侵袭期间，基质在细胞和ECM水平上均显示出活化过程。与体内重复类似，在基质区室中透明质酸和纤连蛋白过表达方面也发现了ECM重塑。此外，以基质组织为特色的细胞组装式ECM可通过实时多光子显微镜在基质激活过程中在线监测胶原蛋白的重塑。而且，已经实时监测了间质室内大分子的运输。通过实时多光子显微镜，可以在线监测基质激活过程中胶原蛋白的重塑。而且，已经实时监测了间质室内大分子的运输。通过实时多光子显微镜，可以在线监测基质激活过程中胶原蛋白的重塑。而且，已经实时监测了间质室内大分子的运输。

更新日期：2016-11-07

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