Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects.
Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects.
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DOI：
10.1039/c0ib00063a
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Beebe DJ
中科院分区：
文献类型：
--
作者：
Sung KE;Yang N;Pehlke C;Keely PJ;Eliceiri KW;Friedl A;Beebe DJ
导管原位癌（DCIS）向浸润性导管癌（IDC）的转变是乳腺癌进展的关键一步。我们引入了一种简单的微流体 3D 区室化系统，其中乳腺上皮细胞 (MCF-DCIS) 与人乳腺成纤维细胞 (HMF) 共培养，这促进了体外从 DCIS 向 IDC 的转变。该模型能够控制微环境中的空间（距离依赖性）和时间（从较大簇的过渡）方面，从而允许以现有实验模型不可行的方式重演体内环境。当 HMF 与 MCF-DCIS 细胞相距一定距离（0.5-1.5 mm）培养时，我们观察到最初的形态变化，表明可溶性因子可以开始转变。然而，细胞间与 HMF 的接触使得 MCF-DCIS 细胞完成向侵袭的转变。独特的是，分隔平台能够分析胶原蛋白固有的二次谐波生成信号，从而提供 DCIS 相关胶原蛋白重塑的无标记定量分析。基于阵列微通道的模型与现有基础设施兼容，并且首次提供了一种具有成本效益的方法来测试 DCIS 进展为 IDC 所涉及途径的抑制剂，从而可以通过筛选方法来识别潜在的治疗靶点。重要的是，该模型可以轻松适应并推广到各种细胞间信号传导研究。
The transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) is a critical step in breast cancer progression. We introduce a simple microfluidic 3D compartmentalized system in which mammary epithelial cells (MCF-DCIS) are co-cultured with human mammary fibroblasts (HMFs), which promotes a transition from DCIS to IDC in vitro. The model enables control of both spatial (distance-dependence) and temporal (transition from larger clusters) aspects within the microenvironment, allowing recapitulation of the in vivo environment in ways not practical with existing experimental models. When HMFs were cultured some distance (0.5-1.5 mm) from the MCF-DCIS cells, we observed an initial morphological change, suggesting soluble factors can begin the transition. However, cell-cell contact with HMFs allowed the MCF-DCIS cells to complete the transition to invasion. Uniquely, the compartmentalized platform enables the analysis of the intrinsic second harmonic generation signal of collagen, providing a label-free quantitative analysis of DCIS-associated collagen remodeling. The arrayed microchannel-based model is compatible with existing infrastructure and, for the first time, provides a cost effective approach to test for inhibitors of pathways involved in DCIS progression to IDC allowing a screening approach to the identification of potential therapeutic targets. Importantly, the model can be easily adapted and generalized to a variety of cell-cell signaling studies.
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DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
DOI：
10.1073/pnas.0308090100
发表时间：
2004-02-03
影响因子：
11.1
作者：
Seton-Rogers, SE;Lu, Y;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
--
作者：
Puccinelli, John P.;Su, Xiaojing;Beebe, David J.
通讯作者：
Beebe, David J.
影响因子：
7.5
作者：
Bryan, BB;Schnitt, SJ;Collins, LC
通讯作者：
Collins, LC
影响因子：
11.2
作者：
Rizki, Aylin;Weaver, Valerie M.;Bissell, Mina J.
通讯作者：
Bissell, Mina J.