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Cadherin- and Rigidity-Dependent Growth of Lung Cancer Cells in a Partially Confined Microenvironment.
Hui, T H; Tang, Y H; Yan, Z; Yip, T C; Fong, H W; Cho, W C; Ngan, K C; Shum, H C; Lin, Y.
Afiliação
  • Hui TH; Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
  • Tang YH; HKU-Shenzhen Institute of Research and Innovation (HKU-SIRI), Kejizhong second Rd., Hi-Tech Industrial Park, Nanshan District, Shenzhen, Guangdong, China.
  • Yan Z; Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
  • Yip TC; Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
  • Fong HW; HKU-Shenzhen Institute of Research and Innovation (HKU-SIRI), Kejizhong second Rd., Hi-Tech Industrial Park, Nanshan District, Shenzhen, Guangdong, China.
  • Cho WC; Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong SAR, China.
  • Ngan KC; Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong SAR, China.
  • Shum HC; Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong SAR, China.
  • Lin Y; Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong SAR, China.
ACS Biomater Sci Eng ; 4(2): 446-455, 2018 Feb 12.
Article em En | MEDLINE | ID: mdl-33418735
During tumor development, cancer cells constantly confront different types of extracellular barriers. However, fundamental questions like whether tumor cells will continue to grow against confinement or away from it and what key factors govern this process remain poorly understood. To address these issues, here we examined the growth dynamics of human lung epithelial carcinoma A549 cells partially confined in micrometer-sized cylindrical pores with precisely controlled wall stiffness. It was found that, after reaching confluency, the cell monolayer enclosed by a compliant wall was able to keep growing and pushing the boundary, eventually leading to a markedly enlarged pore. In contrast, a much reduced in-plane growth and elevated strain level among cells were observed when the confining wall becomes stiff. Furthermore, under such circumstance, cells switched their growth from within the monolayer to along the out-of-plane direction, resulting in cell stacking. We showed that these observations can be well explained by a simple model taking into account the deformability of the wall and the threshold stress for inhibiting cell growth. Interestingly, cadherins were found to play an important role in the proliferation and stress buildup within the cell monolayer by aggregating at cell-cell junctions. The stiff confinement led to an elevated expression level of cadherins. Furthermore, inhibition of N-cadherin resulted in a significantly suppressed cell growth under the same confining conditions.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Pulmao Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: ACS Biomater Sci Eng Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Pulmao Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: ACS Biomater Sci Eng Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China