Leaky blood vessels and cell proliferation within tumors contribute to increased interstitial fluid flow, a phenomenon that is thought to influence the movement of cancer cells and metastasis. Researchers co-led by Ludwig Oxford’s Helen Byrne examined, via mathematical modeling, how the mechanical and chemical landscape around cells might influence the direction of their migration. The interstitial flow creates two opposing forces. One, which the researchers call tensotaxis, draws the cells “upstream”, or against the interstitial flow, as a consequence of their cytoskeletal responses to changes in external pressure. The other, chemotaxis, pulls the cells in the direction of the flow, or “downstream”, in response to flow-induced gradients of chemoattractants that are produced by the moving cell itself and swept along with the interstitial flow. The latter mechanism has been observed in tumors, with cancer cells producing the ligand CCL21 and migrating downstream as the chemoattractant binds their own CCR7 receptors. Studies have also shown that changes in interstitial flow conditions and local cell density can affect these competing stimuli and alter the direction of cell migration. Helen and her colleagues reported in a February paper in the Biophysical Journal a mathematical model that predicts how the balance between these competing mechanisms changes over time and determined the conditions under which cells’ transitions from upstream to downstream migration occur.
Using a probabilistic approach to derive a two-phase model of flow-induced cell migration
Biophysical Journal, 2024 February 26