Dynamics of cancerous tissue correlates with invasiveness

Abstract

Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

Unjamming and collective migration in MCF10A breast cancer cell lines

“…These model systems clearly lack a host of factors that pertain in vivo, most notably immune cells, cancer stem cells, connective tissue, vascularity, and three-dimensionality. Despite these inherent limitations, these reduced cancer model systems have been widely used in a variety of contexts but have remained poorly understood [12,20,[45][46][47][48][49][50][51]. It is interesting, therefore, to determine whether these reduced two-dimensional cell layers retain the cell jamming mechanism that has been established both theoretically [2,11,25] and experimentally in non-cancerous epithelial layers [1,2] as well as in three dimensional cancer organoids [28,35,52].…”

Pore Shape Defines Paths of Metastatic Cell Migration

“…While approaching the parallel barriers, the cells tended to proliferate and aggregate forming multicellular clusters progressing in the same direction . A cell image velocimetry (CIV) analysis of motility in these clusters revealed that MCF10A cells moved with a high correlation typical of connected epithelial cells, prior to making contact with the barriers (Figure S14). − The correlation length indicates that groups of up to 10 cells tended to move coherently within these clusters.…”

Matrix Anisotropy Promotes a Transition of Collective to Disseminated Cell Migration via a Collective Vortex Motion

“…[ 29a ] In contrast, in another study that records the collective cell motion of a larger confluent cell sheet in 6‐well plates, MCF7 and MDAMB231 cells display local collective vortex motion after cell division. [ 31 ] Interestingly, the vorticity is more robust in the more invasive MDAMB231 cells than in weakly invasive MCF7 cells. [ 31 ] The conflicting results of how different cell types and even the same cell type respond to different experimental conditions again highlight that more research is needed to decipher the dynamic and complicated collective motion of cells.…”