Confinement primes cells for faster migration by polarizing active mitochondria
Jenna A Mosier1, Emily D Fabiano1, Catherine M Ludolph2
1Department of Biomedical Engineering, Vanderbilt University Nashville TN USA cynthia.reinhart-king@vanderbilt.edu.
Nanoscale Advances
|December 21, 2023
Summary
Cancer cells primed by confinement in the tumor microenvironment migrate faster, retaining this speed even after exiting confined spaces. This suggests a memory effect influencing future cell migration and metastasis.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Mechanical cues within the tumor microenvironment regulate cancer cell migration.
- Tumor microscale pores create confinement, increasing cell-matrix contact and altering cell behavior.
Purpose of the Study:
- To investigate how confinement in the tumor microenvironment primes MDA-MB-231 breast cancer cells for enhanced migration.
- To understand the role of cellular machinery and memory in post-confinement migration.
Main Methods:
- Utilized a collagen microtrack platform to control cell confinement.
- Observed cancer cell migration speed, cytoskeletal rearrangement, and organelle localization (actin, mitochondria).
- Investigated the effect of confinement memory by transitioning cells from high to low confinement regions.
- Disrupted focal adhesions via vinculin knockout to assess its role.
Main Results:
- Migration through confined tracks increased breast cancer cell speed and accumulated migratory machinery at the cell front.
- Cells maintained high migration speeds even after exiting confinement, indicating a 'memory' of prior conditions.
- Active mitochondria remained localized at the cell front post-confinement.
- Vinculin disruption abolished mitochondrial localization and fast migration after confinement release.
Conclusions:
- Confinement in the tumor microenvironment primes cancer cells for sustained fast migration through a memory mechanism.
- Active mitochondrial localization, dependent on focal adhesions, is crucial for this post-confinement migratory enhancement.
- Understanding these confinement-driven mechanisms could reveal therapeutic targets to inhibit breast cancer metastasis.
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