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A Biomimetic High Throughput Model of Cancer Cell Spheroid Dissemination onto Aligned Fibrillar Collagen
Date Issued
2022-08
Date Available
2022-07-19T08:22:21Z
Abstract
Cell dissemination during tumor development is a characteristic of cancer metastasis. Dissemination from three-dimensional spheroid models on extracellular matrices designed to mimic tissue-specific physiological microenvironments may allow us to better elucidate the mechanism behind cancer metastasis and the response to therapeutic agents. The orientation of fibrillar collagen plays a key role in cellular processes and mediates metastasis through contact-guidance. Understanding how cells migrate on aligned collagen fibrils requires in vitro assays with reproducible and standardized orientation of collagen fibrils on the macro-to-nanoscale. Herein, we implement a spheroid-based migration assay, integrated with a fibrillar type I collagen matrix, in a manner compatible with high throughput image acquisition and quantitative analysis. The migration of highly proliferating U2OS osteosarcoma cell spheroids onto an aligned fibrillar type I collagen matrix were quantified. Cell dissemination from the spheroid was polarized with increased invasion in the direction of fibril alignment. The resulting area of cell dissemination had an aspect ratio of 1.2 ± 0.1 and an angle of maximum invasion distance of 5° ± 44° relative to the direction of collagen fibril alignment. The assay described here can be applied to a fully automated imaging and analysis pipeline for the assessment of tumor cell migration with high throughput screening.
Sponsorship
European Commission Horizon 2020
Science Foundation Ireland
Other Sponsorship
Marie Skłodowska-Curie
UCD School of Physics (SIRAT − Scholarship in Research and Teaching)
Sustainable Energy Authority of Ireland (SEAI)
Type of Material
Journal Article
Publisher
Elsevier
Journal
SLAS Technology
Volume
27
Issue
4
Start Page
267
End Page
275
Copyright (Published Version)
2022 The Authors
Language
English
Status of Item
Peer reviewed
ISSN
2472-6303
This item is made available under a Creative Commons License
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