10.17867/10000163A
Lee, Rachel
Rachel
Lee
https://orcid.org/0000-0001-9359-0422
University of Maryland, Baltimore
Martin, Stuart
Stuart
Martin
https://orcid.org/0000-0002-4378-4381
Distinct Roles of Tumor Associated Mutations in Collective Cell Migration
University of Dundee
2021
Image
FOS: Biological sciences
FOS: Biological sciences
Vitolo, Michele
Michele
Vitolo
https://orcid.org/0000-0001-8055-9645
University of Maryland, Baltimore
Losert, Wolfgang
Wolfgang
Losert
https://orcid.org/0000-0002-1792-7860
University of Maryland, Baltimore
2021-06-21
2021
en
10.1038/s41598-021-89130-6
33986306
ome.tiff
Creative Commons Attribution 4.0 International
Recent evidence suggests that groups of cells are more likely to form clinically dangerous metastatic tumors, emphasizing the importance of understanding mechanisms underlying collective behavior. The emergent collective behavior of migrating cell sheets in vitro has been shown to be disrupted in tumorigenic cells but the connection between this behavior and in vivo tumorigenicity remains unclear. We use particle image velocimetry to measure a multidimensional migration phenotype for genetically defined human breast epithelial cell lines that range in their in vivo behavior from non-tumorigenic to aggressively metastatic. By using cells with controlled mutations, we show that PTEN deletion enhances collective migration, while Ras activation suppresses it, even when combined with PTEN deletion. These opposing effects on collective migration of two mutations that are frequently found in patient tumors could be exploited in the development of novel treatments for metastatic disease. Our methods are based on label-free phase contrast imaging, and thus could easily be applied to patient tumor cells. The short time scales of our approach do not require potentially selective growth, and thus in combination with label-free imaging would allow multidimensional collective migration phenotypes to be utilized in clinical assessments of metastatic potential.
MCF10A, PTEN-/-, KRas, and KRas/PTEN-/- cell lines or the MCF10A and MDA-MB-231 cell lines were plated in a collective migration assay that uses circular cell sheets. Tiled images of each full cell sheet were taken before and after a set of time lapse images was taken of two ROIs in each cell sheet.
National Institutes of Health
https://doi.org/10.13039/100000002
T32-CA154274
Training Grant in Cancer Biology
National Institutes of Health
https://doi.org/10.13039/100000002
R01-CA154624
Targeting microtubule stabilization to reduce breast tumor metastasis
National Institutes of Health
https://doi.org/10.13039/100000002
R01-CA124704
Tubulin microtentacles in detached mammary epithelial cells
Air Force Office of Scientific Research
https://doi.org/10.13039/100000181
FA9550-16-1-0052
National Institutes of Health
https://doi.org/10.13039/100000002
I01-BX002746
Rapid analysis of patient tumor cell drug responses to reduce metastatic risk