Regulators of Metastasis Modulate the Migratory Response to Cell Contact under Spatial Confinement

Biophysical Journal
Daniel F MilanoAnand R Asthagiri

Abstract

The breast tumor microenvironment (TMEN) is a unique niche where protein fibers help to promote invasion and metastasis. Cells migrating along these fibers are constantly interacting with each other. How cells respond to these interactions has important implications. Cancer cells that circumnavigate or slide around other cells on protein fibers take a less tortuous path out of the primary tumor; conversely, cells that turn back upon encountering other cells invade less efficiently. The contact response of migrating cancer cells in a fibrillar TMEN is poorly understood. Here, using high-aspect ratio micropatterns as a model fibrillar platform, we show that metastatic cells overcome spatial constraints to slide effectively on narrow fiber-like dimensions, whereas nontransformed MCF-10A mammary epithelial cells require much wider micropatterns to achieve moderate levels of sliding. Downregulating the cell-cell adhesion protein, E-cadherin, enables MCF-10A cells to slide on narrower micropatterns; meanwhile, introducing exogenous E-cadherin in metastatic MDA-MB-231 cells increases the micropattern dimension at which they slide. We propose the characteristic fibrillar dimension (CFD) at which effective sliding is achieved as a metri...Continue Reading

References

Sep 3, 2016·Cell Adhesion & Migration·Sangyoon J HanNathan J Sniadecki
Oct 6, 2016·Biophysical Journal·Daniel F MilanoAnand R Asthagiri
Dec 17, 2016·PLoS Computational Biology·Dirk Alexander KulawiakWouter-Jan Rappel
Oct 11, 2017·Journal of Physics D: Applied Physics·Brian A Camley, Wouter-Jan Rappel
May 12, 2020·Frontiers in Physiology·Mary T DoolinKimberly M Stroka
Oct 21, 2016·Cellular and Molecular Bioengineering·Mark L LalliAnand R Asthagiri
Feb 6, 2020·Breast Cancer Research and Treatment·Daniel DiCorpoJames Michaelson
Jul 19, 2020·Acta Neuropathologica Communications·Kyungmin KoMetin Ozdemirli

Citations

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Related Concepts

Protrusion
Recombinant Transforming Growth Factor
ErbB-2 Receptor
PARD3
In Vivo
Biochemical Pathway
Subfamily lentivirinae
Transforming Growth Factor beta
Tumor Suppressor Genes
Specimen Type - Fibroblasts

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