Bouzos Evangelia, Asuri Prashanth
Department of Bioengineering, Santa Clara University, Santa Clara, CA 95053, USA.
Cancers (Basel). 2023 Mar 12;15(6):1729. doi: 10.3390/cancers15061729.
Given the key role of cell migration in cancer metastasis, there is a critical need for in vitro models that better capture the complexities of in vivo cancer cell microenvironments. Using both two-dimensional (2D) and three-dimensional (3D) culture models, recent research has demonstrated the role of both matrix and ligand densities in cell migration. Here, we leveraged our previously developed 2.5D sandwich culture platform to foster a greater understanding of the adhesion-dependent migration of glioblastoma cells with a stiffness gradient. Using this model, we demonstrated the differential role of stiffness gradients in migration in the presence and absence of adhesion moieties. Furthermore, we observed a positive correlation between the density of cell adhesion moieties and migration, and a diminished role of stiffness gradients at higher densities of adhesion moieties. These results, i.e., the reduced impact of stiffness gradients on adhesion-dependent migration relative to adhesion-independent migration, were confirmed using inhibitors of both mechanotransduction and cell adhesion. Taken together, our work demonstrates the utility of sandwich culture platforms that present stiffness gradients to study both adhesion-dependent and -independent cell migration and to help expand the existing portfolio of in vitro models of cancer metastasis.
鉴于细胞迁移在癌症转移中起着关键作用，迫切需要能更好地捕捉体内癌细胞微环境复杂性的体外模型。利用二维（2D）和三维（3D）培养模型，最近的研究已经证明了基质和配体密度在细胞迁移中的作用。在此，我们利用我们之前开发的2.5D三明治培养平台，以更深入地了解具有刚度梯度的胶质母细胞瘤细胞的黏附依赖性迁移。使用该模型，我们证明了在存在和不存在黏附部分的情况下，刚度梯度在迁移中的不同作用。此外，我们观察到细胞黏附部分的密度与迁移之间呈正相关，并且在较高密度的黏附部分时，刚度梯度的作用减弱。使用机械转导和细胞黏附的抑制剂证实了这些结果，即相对于非黏附依赖性迁移，刚度梯度对黏附依赖性迁移的影响降低。综上所述，我们的工作证明了呈现刚度梯度的三明治培养平台在研究黏附依赖性和非黏附依赖性细胞迁移以及帮助扩展现有癌症转移体外模型组合方面的实用性。
