Division Induced Dynamics In Non-Invasive And Invasive Breast Cancer

BIOPHYSICAL JOURNAL(2017)

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摘要
Cancerous cells pose a great threat when they gain the ability to metastasize, but little is known on why some cells gain the ability to invade adjacent tissue while other cells are restricted to the primary tumor. We have approached this topic by experimentally characterizing the division induced dynamics of invasive and non-invasive breast cancer monolayers using human and murine model systems. Particle image velocimetry measurements of intrinsic velocities surrounding a dividing cell reveal a strong relation between tissue dynamics, such as vorticity and divergence, and the invasive potential of the cell type. When a cell divides we observe two distinct vortex pairs in the vorticity field surrounding the dividing cell. Analyzing images over longer time scales reveals no long range interactions between the cancerous cells, and the interactions observed surrounding a dividing cell are constricted to under one cell diameter away from the point of cytokinesis. This is to be expected as cancer cells are known to have decreased cell-to-cell interactions compared to healthy cells. An increased intensity in the dynamics (velocity, vorticity and divergence) of invasive monolayers compared to their non-invasive counterparts, is apparent for both human and murine cell lines. These dynamics can be simulated using a continuum model, and from this we extract the characteristic force exerted by a dividing cell on the neighboring cells. These values reveal a correlation between the force and the invasiveness of the breast cancer cells. Together, the model and experimental data suggest a correlation between the dynamical properties of cells and their invasive potential. Further study of the difference in dynamics between invasive and non-invasive cancers could help us understand the mechanisms governing metastasis.
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