Lee, Geonhee Cho, Youngbin Kim, Eun Hye Choi, Jong Min Chae, Soo Sang Lee, Min-Goo Kim, Jonghyun Choi, Won Jin Kwon, Joseph Han, Eun Hee Kim, Seong Hwan Park, Sungsu Chung, Young-Ho Chi, Sung-Gil Jung, Byung Hwa Shin, Jennifer H. Lee, Jeong-O 2024-01-19T13:01:45Z 2024-01-19T13:01:45Z 2022-02-17 2022-01 1944-8244 https://pubs.kist.re.kr/handle/201004/115854 Tissue microarchitecture imposes physical constraints to the migration of individual cells. Especially in cancer metastasis, three-dimensional structural barriers within the extracellular matrix are known to affect the migratory behavior of cells, regulating the pathological state of the cells. Here, we employed a culture platform with micropillar arrays of 2 mu m diameter and 16 mu m pitch (2.16 micropillar) as a mechanical stimulant. Using this platform, we investigated how a long-term culture of A549 human lung carcinoma cells on the (2.16) micropillar-embossed dishes would influence the pathological state of the cell. A549 cells grown on the (2.16) micropillar array with 10 mu m height exhibited a significantly elongated morphology and enhanced migration even after the detachment and reattachment, as evidenced in the conventional wound-healing assay, single-cell tracking analysis, and in vivo tumor colonization assays. Moreover, the pillar-induced morphological deformation in nuclei was accompanied by cell-cycle arrest in the S phase, leading to suppressed proliferation. While these marked traits of morphology- migration-proliferation support more aggressive characteristics of metastatic cancer cells, typical indices of epithelial-mesenchymal transition were not found, but instead, remarkable traces of amoeboidal transition were confirmed. Our study also emphasizes the importance of mechanical stimuli from the microenvironment during pathogenesis and how gained traits can be passed onto subsequent generations, ultimately affecting their pathophysiological behavior. Furthermore, this study highlights the potential use of pillar-based mechanical stimuli as an in vitro cell culture strategy to induce more aggressive tumorigenic cancer cell models. English American Chemical Society Pillar-Based Mechanical Induction of an Aggressive Tumorigenic Lung Cancer Cell Model Article 10.1021/acsami.1c12380 1 ACS Applied Materials & Interfaces, v.14, no.1, pp.20 - 31 ACS Applied Materials & Interfaces 14 1 20 31 N scie scopus 000733782600001 2-s2.0-85121914691 Nanoscience & Nanotechnology Materials Science, Multidisciplinary Science & Technology - Other Topics Materials Science Article; Early Access TOPOGRAPHICAL CONTROL MIGRATION ADHESION DIFFERENTIATION CONTRACTILITY BEHAVIOR KEYWORDS micropillar array A549 amoeboid migration mechanical stimuli cancer cell