Department of Biological and Environmental Engineering, 306 Riley-Robb Hall, Cornell University, Ithaca, NY 14853, United States of America.
Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, United States of America.
Phys Biol. 2022 Mar 10;19(3). doi: 10.1088/1478-3975/ac54c7.
Epidermal growth factor (EGF), a potent cytokine, is known to promote tumor invasion bothand. 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.
表皮生长因子（EGF）是一种有效的细胞因子，已知它既能促进肿瘤侵袭，又能促进肿瘤侵袭。此前，我们观察到，在微流控平台上，在存在线性 EGF 梯度的情况下，嵌入 3D 胶原基质中的单个乳腺癌细胞（MDA-MB-231 细胞系）表现出增强的迁移能力，但没有明显的趋化性。受最近一个理论发展的启发，即聚集的哺乳动物细胞对化学梯度的反应不同于单个细胞，我们研究了在 EGF 梯度存在的情况下，肿瘤球体在 3D 细胞外基质（ECM）中的侵袭。我们发现，EGF 梯度促进了肿瘤细胞从球体核心的脱离，并且肿瘤球体核心的位置对 EGF 梯度表现出轻微的趋化反应。对于那些从球体中脱离的肿瘤细胞，它们表现出增强的迁移反应，与以前使用嵌入 ECM 中的单个细胞进行的实验结果相反。对于球体核心之外的细胞，没有发现对 EGF 梯度的明显趋化反应。这项工作表明，一簇肿瘤细胞对 EGF 梯度的反应不同于单个肿瘤细胞，并且突出了肿瘤球体平台在肿瘤侵袭研究中的重要性。
