Hong Xiao, Xu Yuanhao, Pang Stella W
Department of Electrical Engineering and Centre for Biosystems, Neuroscience and Nanotechnology, City University of Hong Kong, Kowloon, Hong Kong, China.
Lab Chip. 2023 Jan 31;23(3):511-524. doi: 10.1039/d2lc00616b.
The three-dimensional (3D) structure of the extracellular matrix and cell-cell contacts are two important cues to altering cell migration behavior and the tumor formation process. In this work, we designed and fabricated microwell arrays with a grating-patterned bottom in polydimethylsiloxane platforms to systematically study the effects of confinement, changes in topography, and cell-cell contacts on the migration behavior of nasopharyngeal carcinoma (NPC43) and immortalized nasopharyngeal epithelial (NP460) cells by time-lapse imaging. When two types of cells were co-cultured in microwells, the migration speed and spreading area of NPC43 cells were significantly increased, which might be attributed to the heterotypic cell-cell contacts with NP460 cells. On a flat surface, NPC43 cells could not form clusters due to the frequent interruptions by the active movements of NP460 cells. However, in 3D microwell arrays, clusters of NPC43 cells formed on the bottom surface while the majority of NP460 cells migrated onto the sidewalls. These cell clusters could be further processed to form spheroids for drug screening. These results also revealed that the 3D microenvironments and cell-cell contacts could have significant implications for NPC cell migration and initiation of tumor formation, which will provide insight for NPC progression and dissemination.
细胞外基质的三维（3D）结构和细胞间接触是改变细胞迁移行为和肿瘤形成过程的两个重要线索。在这项工作中，我们在聚二甲基硅氧烷平台上设计并制造了底部具有光栅图案的微孔阵列，通过延时成像系统地研究限制、地形变化和细胞间接触对鼻咽癌（NPC43）和永生化鼻咽上皮（NP460）细胞迁移行为的影响。当两种类型的细胞在微孔中共同培养时，NPC43细胞的迁移速度和铺展面积显著增加，这可能归因于与NP460细胞的异型细胞间接触。在平坦表面上，由于NP460细胞的活跃运动频繁干扰，NPC43细胞无法形成簇。然而，在3D微孔阵列中，NPC43细胞簇在底表面形成，而大多数NP460细胞迁移到侧壁上。这些细胞簇可以进一步处理形成球体用于药物筛选。这些结果还表明，3D微环境和细胞间接触可能对NPC细胞迁移和肿瘤形成起始具有重要意义，这将为NPC的进展和扩散提供见解。
