Tumor spheroid invasion in epidermal growth factor gradients revealed by a 3D microfluidic device

被引:6
|
作者
Suh, Young Joon [1 ]
Pandey, Mrinal [1 ]
Segall, Jeffrey E. [2 ]
Wu, Mingming [1 ]
机构
[1] Cornell Univ, Dept Biol & Environm Engn, 306 Riley Robb Hall, Ithaca, NY 14853 USA
[2] Albert Einstein Coll Med, Anat & Struct Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA
关键词
tumor spheroid; chemotaxis; microfluidics; EGF; invasion; 3D ECM; tumor microenvironment; COLLECTIVE MIGRATION; FACTOR RECEPTOR; CANCER-CELLS; CHEMOTAXIS; EXPRESSION; PEPTIDES; PROMOTES; MOTILITY;
D O I
10.1088/1478-3975/ac54c7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epidermal growth factor (EGF), a potent cytokine, is known to promote tumor invasion both in vivo and in vitro. Previously, we observed that single breast tumor cells (MDA-MB-231 cell line) embedded within a 3D collagen matrix displayed enhanced motility but no discernible chemotaxis in the presence of linear EGF gradients using a microfluidic platform. Inspired by a recent theoretical development that clustered mammalian cells respond differently to chemical gradients than single cells, we studied tumor spheroid invasion within a 3D extracellular matrix (ECM) in the presence of EGF gradients. We found that EGF gradients promoted tumor cell detachment from the spheroid core, and the position of the tumor spheroid core showed a mild chemotactic response towards the EGF gradients. For those tumor cells detached from the spheroids, they showed an enhanced motility response in contrast to previous experimental results using single cells embedded within an ECM. No discernible chemotactic response towards the EGF gradients was found for the cells outside the spheroid core. This work demonstrates that a cluster of tumor cells responds differently than single tumor cells towards EGF gradients and highlights the importance of a tumor spheroid platform for tumor invasion studies.
引用
收藏
页数:10
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