scholarly journals Cancer cells resist mechanical destruction in the circulation via RhoA-myosin II axis

2019 ◽  
Author(s):  
Devon L. Moose ◽  
Benjamin L. Krog ◽  
Lei Zhao ◽  
Tae-Hyung Kim ◽  
Sophia Williams-Perez ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cancer Cells ◽  
Mouse Models ◽  
Fluid Shear Stress ◽  
Myosin Ii ◽  
Membrane Damage ◽  
Fluid Shear ◽  
Mechanical Destruction ◽  
Primary Tumors ◽  
Hemodynamic Forces

ABSTRACTDuring metastasis cancer cells are exposed to potentially destructive hemodynamic forces including fluid shear stress (FSS) whileen routeto distant sites. However, prior work indicates that cancer cells are more resistant to brief pulses of high-level fluid shear stress (FSS)in vitrorelative to non-transformed epithelial cells. Herein we identify a mechanism of FSS resistance in cancer cells, and extend these findings to mouse models of circulating tumor cells (CTCs). We show that cancer cells acutely isolated from primary tumors are resistant to FSS. Our findings demonstrate that cancer cells activate the RhoA-myosin II axis in response to FSS, which protects them from FSS-induced plasma membrane damage. Moreover, we show that the myosin II activity is protective to CTCs in mouse models. Collectively our data indicate that viable CTCs actively resist destruction by hemodynamic forces and are likely to be more mechanically robust than is commonly thought.

scholarly journals Macrorheology and adaptive microrheology of endothelial cells subjected to fluid shear stress

2007 ◽  
Vol 293 (5) ◽  
pp. C1568-C1575 ◽  
Author(s):  
Jhanvi H. Dangaria ◽  
Peter J. Butler
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cells ◽  
Step Change ◽  
Time Dependent ◽  
Creep Function ◽  
Fluid Shear ◽  
Hemodynamic Forces ◽  
Forcing Function

Vascular endothelial cells (ECs) respond to temporal and spatial characteristics of hemodynamic forces by alterations in their adhesiveness to leukocytes, secretion of vasodilators, and permeability to blood-borne constituents. These physiological and pathophysiological changes are tied to adaptation of cell mechanics and mechanotransduction, the process by which cells convert forces to intracellular biochemical signals. The exact time scales of these mechanical adaptations, however, remain unknown. We used particle-tracking microrheology to study adaptive changes in intracellular mechanics in response to a step change in fluid shear stress, which simulates both rapid temporal and steady features of hemodynamic forces. Results indicate that ECs become significantly more compliant as early as 30 s after a step change in shear stress from 0 to 10 dyn/cm2followed by recovery of viscoelastic parameters within 4 min of shearing, even though shear stress was maintained. After ECs were sheared for 5 min, return of shear stress to 0 dyn/cm2in a stepwise manner did not result in any further rheological adaptation. Average vesicle displacements were used to determine time-dependent cell deformation and macrorheological parameters by fitting creep function to a linear viscoelastic liquid model. Characteristic time and magnitude for shear-induced deformation were 3 s and 50 nm, respectively. We conclude that ECs rapidly adapt their mechanical properties in response to shear stress, and we provide the first macrorheological parameters for time-dependent deformations of ECs to a physiological forcing function. Such studies provide insight into pathologies such as atherosclerosis, which may find their origins in EC mechanics.

scholarly journals Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor

2019 ◽  
Vol 116 (11) ◽  
pp. 3084-3097 ◽  
Author(s):  
Caymen M. Novak ◽  
Eric N. Horst ◽  
Charles C. Taylor ◽  
Catherine Z. Liu ◽  
Geeta Mehta
Keyword(s):  
Breast Cancer ◽  
Shear Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Fluid Shear Stress ◽  
Fluid Shear

scholarly journals Cellular Mechanisms of Circulating Tumor Cells During Breast Cancer Metastasis

2020 ◽  
Vol 21 (14) ◽  
pp. 5040 ◽  
Author(s):  
Han-A Park ◽  
Spenser R. Brown ◽  
Yonghyun Kim
Keyword(s):  
Breast Cancer ◽  
Shear Stress ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Fluid Shear Stress ◽  
Breast Cancer Metastasis ◽  
Fluid Shear ◽  
Cellular Mechanisms

Circulating tumor cells (CTCs) are cancer cells that detach from the primary site and travel in the blood stream. A higher number of CTCs increases the risk of breast cancer metastasis, and it is inversely associated with the survival rates of patients with breast cancer. Although the numbers of CTCs are generally low and the majority of CTCs die in circulation, the survival of a few CTCs can seed the development of a tumor at a secondary location. An increasing number of studies demonstrate that CTCs undergo modification in response to the dynamic biophysical environment in the blood due in part to fluid shear stress. Fluid shear stress generates reactive oxygen species (ROS), triggers redox-sensitive cell signaling, and alters the function of intracellular organelles. In particular, the mitochondrion is an important target organelle in determining the metastatic phenotype of CTCs. In healthy cells, mitochondria produce adenosine triphosphate (ATP) via oxidative phosphorylation in the electron transport chain, and during oxidative phosphorylation, they produce physiological levels of ROS. Mitochondria also govern death mechanisms such as apoptosis and mitochondrial permeability transition pore opening to, in order eliminate unwanted or damaged cells. However, in cancer cells, mitochondria are dysregulated, causing aberrant energy metabolism, redox homeostasis, and cell death pathways that may favor cancer invasiveness. In this review, we discuss the influence of fluid shear stress on CTCs with an emphasis on breast cancer pathology, then discuss alterations of cellular mechanisms that may increase the metastatic potentials of CTCs.

In Situ Monitoring of Fluid Shear Stress Enhanced Adherence of Bacteria to Cancer Cells on Microfluidic Chip

2019 ◽  
Vol 91 (9) ◽  
pp. 5973-5979 ◽  
Author(s):  
Wanling Zhang ◽  
Sifeng Mao ◽  
Ziyi He ◽  
Zengnan Wu ◽  
Jin-Ming Lin
Keyword(s):  
Shear Stress ◽  
Cancer Cells ◽  
Microfluidic Chip ◽  
Fluid Shear Stress ◽  
In Situ Monitoring ◽  
Fluid Shear

scholarly journals Fluid shear stress-induced IL-8/CXCR signaling in human ovarian cancer cells

2019 ◽  
Vol 8 (4) ◽  
pp. 1591-1601
Author(s):  
Lei Sun ◽  
Jirui Wen ◽  
Ling Wang ◽  
Qiao Wen ◽  
Jiang Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Shear Stress ◽  
Cancer Cells ◽  
Fluid Shear Stress ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Fluid Shear

scholarly journals Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death

2021 ◽  
Vol 134 (4) ◽  
pp. jcs251470
Author(s):  
Jacob M. Hope ◽  
Matthew R. Bersi ◽  
Jenna A. Dombroski ◽  
Andrea B. Clinch ◽  
Rebecca S. Pereles ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Shear Stress ◽  
Cell Lines ◽  
Fluid Shear Stress ◽  
Membrane Damage ◽  
Fluid Shear ◽  
Membrane Repair ◽  
Cell Membrane Damage

ABSTRACTCirculating tumor cells (CTCs) are exposed to fluid shear stress (FSS) of greater than 1000 dyn/cm2 (100 Pa) in circulation. Normally, CTCs that are exposed to FSS of this magnitude die. However, some CTCs develop resistance to this FSS, allowing them to colonize distant organs. We explored how prostate CTCs can resist cell death in response to forces of this magnitude. The DU145, PC3 and LNCaP human prostate cancer cell lines were used to represent cells of different metastatic origins. The cell lines were briefly treated with an average FSS of 3950 dyn/cm2 (395 Pa) using a 30 G needle and a syringe pump. DU145 cells had no change in cell viability, PC3 cells had some cell death and LNCaP cells exhibited significant cell death. These cell death responses correlated with increased cell membrane damage, less efficient membrane repair and increased stiffness. Additionally, FSS treatment prevented the LNCaP FSS-sensitive cell line from forming a growing tumor in vivo. This suggests that these properties play a role in FSS resistance and could represent potential targets for disrupting blood-borne metastasis.

Sign in / Sign up

Export Citation Format

Share Document