Pillar-Based Mechanical Induction of an Aggressive Tumorigenic Lung Cancer Cell Model

Geonhee Lee, Youngbin Cho, Eun Hye Kim, Jong Min Choi, Soo Sang Chae, Min Goo Lee, Jonghyun Kim, Won Jin Choi, Joseph Kwon, Eun Hee Han, Seong Hwan Kim, Sungsu Park, Young Ho Chung, Sung Gil Chi, Byung Hwa Jung, Jennifer H. Shin, Jeong O. Lee

Research output: Contribution to journalArticlepeer-review

Abstract

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 μm diameter and 16 μm 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 μm 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.

Original languageEnglish
Pages (from-to)20-31
Number of pages12
JournalACS Applied Materials and Interfaces
Volume14
Issue number1
DOIs
Publication statusPublished - 2022 Jan 12

Keywords

  • A549
  • amoeboid migration
  • cancer cell
  • mechanical stimuli
  • micropillar array

ASJC Scopus subject areas

  • Materials Science(all)

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