Tumor cells disseminate to distant organs mainly through blood circulation in which they experience considerable levels of fluid shear stress. However, the effects of hemodynamic shear stress on biophysical properties and functions of
circulating tumor cells (CTCs) in
suspension are not fully understood. In this study, we found that the majority of suspended
breast tumor cells could be eliminated by fluid shear stress, whereas cancer stem cells held survival advantages over conventional
cancer cells. Compared to untreated cells,
tumor cells surviving shear stress exhibited unique biophysical properties: 1) cell adhesion was significantly retarded, 2) these cells exhibited elongated morphology and enhanced spreading and expressed genes related to epithelial-mesenchymal transition or hybrid phenotype, and 3) surviving
tumor cells showed reduced
F-actin assembly and stiffness. Importantly, inhibiting
actomyosin activity promoted the survival of suspended
tumor cells in fluid shear stress, whereas activating
actomyosin suppressed cell survival, which might be explained by the up- and downregulation of the antiapoptosis genes. Soft surviving
tumor cells held survival advantages in shear flow and higher resistance to
chemotherapy. Inhibiting
actomyosin activity in untreated cells enhanced chemoresistance, whereas activating
actomyosin in surviving
tumor cells suppressed this ability. These findings might be associated with the corresponding changes in the genes related to multidrug resistance. In summary, these data demonstrate that hemodynamic shear stress significantly influences biophysical properties and functions of suspended
tumor cells. Our study unveils the regulatory roles of
actomyosin in the survival and drug resistance of suspended
tumor cells in hemodynamic shear flow, which suggest the importance of fluid shear stress and
actomyosin activity in
tumor metastasis. These findings may reveal a new, to our knowledge, mechanism by which CTCs are able to survive hemodynamic shear stress and
chemotherapy and may offer a new potential strategy to target CTCs in shear flow and combat chemoresistance through
actomyosin.