Breast Fibroblasts and ECM Components Modulate Breast Cancer Cell Migration through the Secretion of MMPs in a 3D Microfluidic Co-Culture Model

被引:66
|
作者
Lugo-Cintron, Karina M. [1 ,2 ,3 ]
Gong, Max M. [3 ,4 ]
Ayuso, Jose M. [2 ,3 ]
Tomko, Lucas A. [5 ]
Beebe, David J. [1 ,2 ,3 ]
Virumbrales-Munoz, Maria [2 ,3 ]
Ponik, Suzanne M. [3 ,5 ]
机构
[1] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53705 USA
[2] Univ Wisconsin, Dept Pathol & Lab Med, 1111 Highland Ave, Madison, WI 53705 USA
[3] Univ Wisconsin, Wisconsin Inst Med Res, Carbone Canc Ctr, 1111 Highland Ave, Madison, WI 53705 USA
[4] Trine Univ, Dept Biomed Engn, Angola, IN 46703 USA
[5] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53705 USA
基金
加拿大自然科学与工程研究理事会;
关键词
ECM composition; breast Cancer; 3D collagen; microfluidics; organotypic; fibronectin; EXTRACELLULAR-MATRIX COMPONENTS; TUMOR MICROENVIRONMENT; IN-VITRO; FIBRONECTIN EXPRESSION; ACTIVATION; INVASION; METALLOPROTEINASES; TRIAL; MARIMASTAT; THERAPY;
D O I
10.3390/cancers12051173
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The extracellular matrix (ECM) composition greatly influences cancer progression, leading to differential invasion, migration, and metastatic potential. In breast cancer, ECM components, such as fibroblasts and ECM proteins, have the potential to alter cancer cell migration. However, the lack of in vitro migration models that can vary ECM composition limits our knowledge of how specific ECM components contribute to cancer progression. Here, a microfluidic model was used to study the effect of 3D heterogeneous ECMs (i.e., fibroblasts and different ECM protein compositions) on the migration distance of a highly invasive human breast cancer cell line, MDA-MB-231. Specifically, we show that in the presence of normal breast fibroblasts, a fibronectin-rich matrix induces more cancer cell migration. Analysis of the ECM revealed the presence of ECM tunnels. Likewise, cancer-stromal crosstalk induced an increase in the secretion of metalloproteinases (MMPs) in co-cultures. When MMPs were inhibited, migration distance decreased in all conditions except for the fibronectin-rich matrix in the co-culture with human mammary fibroblasts (HMFs). This model mimics the in vivo invasion microenvironment, allowing the examination of cancer cell migration in a relevant context. In general, this data demonstrates the capability of the model to pinpoint the contribution of different components of the tumor microenvironment (TME).
引用
收藏
页数:19
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