Interstitial flows promote amoeboid over mesenchymal motility of breast cancer cells revealed by a three dimensional microfluidic model

摘要: Malignant tumors are often associated with an elevated fluid pressure due to the abnormal growth of vascular vessels, and thus increased interstitial flow out tumors. Recent in vitro works revealed that flows critically regulated tumor cell migration within a three dimensional biomatrix, breast cancer behavior depended sensitively on seeding density, chemokine availability rates. In this paper, we focus role modulating heterogeneity motility phenotype biomatrix. Using newly developed microfluidic model, show cells (MDA-MB-231) embedded 3D type I collagen matrix exhibit both amoeboid mesenchymal motility, promote population towards phenotype. Furthermore, addition exogenous adhesion molecules (fibronectin) extracellular (type collagen) partially rescues presence flow. Quantitative analysis tracks shapes shows distinct differential characteristics cells. Notably, fastest moving belong subpopulation Together, these findings highlight important biophysical forces plasticity, as well suitability models interrogating dynamics at single-cell level.