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The metastasis of solid tumors hinges on cancer cells navigating through complex three-dimensional tissue environments, characterized by mechanical heterogeneity and biological diversity. This process is closely linked to the dynamic migration behavior exhibited by cancer cells, which dictates the invasiveness of tumors. In our study, we investigate tumor spheroids composed of breast cancer cells embedded in three-dimensional (3D) collagen matrices. Through a combination of quantitative experiments, artificial-intelligence-driven image processing, and mathematical modeling, we uncover rapid transitions in cell phenotypes and phenotype-dependent motility among disseminating cells originating from tumor spheroids. Persistent invasion leads to continuous remodeling of the extracellular matrix surrounding the spheroids, altering the landscape of migration phenotypes. Consequently, filopodial cells emerge as the predominant phenotype across diverse extracellular matrix conditions. Our findings unveil the complex mesoscale dynamics of invading tumor spheroids, shedding light on the complex interplay between migration phenotype plasticity, microenvironment remodeling, and cell motility within 3D extracellular matrices. Published by the American Physical Society2024
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2D or 3D? How cell motility measurements are conserved across dimensions in vitro and translate in vivo
Abstract Cell motility is a critical aspect of several processes, such as wound healing and immunity; however, it is dysregulated in cancer. Current limitations of imaging tools make it difficult to study cell migrationin vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D (two‐dimensional) and 3D (three‐dimensional) tissue model systems in which to study cell motilityin vitro, with the aim of mimicking elements of the environments in which cells movein vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries or systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, metrics are conserved across systems. To our surprise, only one metric of cell movement on 2D surfaces significantly and positively correlates with cell migration in 3D environments (percent migrating cells), and cell invasion in 3D has a weak, negative correlation with glioblastoma invasionin vivo. Finally, to compare across complex model systems,in vivodata, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.
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- Award ID(s):
- 1454806
- PAR ID:
- 10459465
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Bioengineering & Translational Medicine
- Volume:
- 5
- Issue:
- 1
- ISSN:
- 2380-6761
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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