Abstract
Cancer cells in the tumor microenvironment and in the metastatic cascade leverage their different intrinsic and extrinsic properties to overcome the confined barriers of the metastatic cascade during metastasis. Although various studies have focused on cell migration under confinement, how the heterogeneity in the stiffness levels of single lung cancer cells affects their migration into confined spaces and the growth of tumor spheroids of confined space migrating cells remains unknown. This study explores how cancer cells with varying stiffness levels steer confined spaces and form post-migration tumor spheroids. Using a single-cell migration platform and a confined trans-well migration setup, the research uncovers that lung cancer cells with lower stiffness and reduced VIM expression exhibit selective migration into confined spaces. These cells, forming irregularly shaped spheroids post-migration, display nuclear shape deformation and downregulated VIM and LMNA genes linked to cell and nuclear stiffness. The findings highlight the heterogeneity of cancer cell migration in confined environments and the subsequent growth of tumor spheroids.
Data availability
Yes, I have research data to declare.The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
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Funding
This research work was supported by grants from the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project (HZQB-KCZYZ-2021017) and City University of Hong Kong (project # 9680217 and 9610559).
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MKA conceived the idea, performed the experiments, analyzed the data, prepared figures, and wrote the manuscript. YM* supervised the project, revised, corrected, and improved the manuscript’s draft. YM and ZJ revised the manuscript and provided insightful comments and suggestions. ZH helped during the experiment by giving suggestions. YC and NY helped analyze the single-cell open array data.
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Alam, M.K., Ma, Y., Zhai, J. et al. Mechano-stress endorsing heterogeneous lung cancer cells migration into confined channels and investigating tumor spheroids growth of confined space migrating cells. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35818-6
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DOI: https://doi.org/10.1038/s41598-026-35818-6
