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Spatial distribution of motile cells within primary tumors

Determine whether motile cells in primary tumors are formed randomly throughout the tumor or instead concentrate within specific subdomains of the tumor, and ascertain the spatial formation pattern at the onset of clustering to inform modeling and interpretation of cluster dynamics.

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Background

The paper models a heterogeneous 2D confluent tumor layer using the Cellular Potts Model, with motile (mesenchymal-like) and non-motile (epithelial-like) cells. To address uncertainty about where motile cells initially appear within a tumor, simulations were run with both random motile-cell distributions and a single strongly aligned motile cluster.

Although the authors verified that, in their simulations, the long-time steady-state clustering did not depend on the initial motile-cell distribution, the actual spatial formation pattern of motile cells in real primary tumors remains unknown. Resolving this uncertainty is important for connecting model assumptions to biological reality and for understanding the initiation and early evolution of collective cluster formation relevant to metastasis.

References

Since we do not know a priori where the motile cells are formed and whether they are formed randomly in space or concentrate in a small subdomain of the primary tumor, we also ran simulations with a different initial condition in which all motile cells start as a single strongly aligned cluster.

Formation of motile cell clusters in heterogeneous model tumors: the role of cell-cell alignment (2406.14196 - Braat et al., 20 Jun 2024) in Materials and methods, Simulation details