Fluid shear stress impacts ovarian cancer cell viability, subcellular organization, and promotes genomic instability

Abstract

Ovarian cancer cells are exposed to physical stress in the peritoneal cavity during both tumor growth and dissemination. Ascites build-up in metastatic ovarian cancer further increases the exposure to fluid shear stress. Here, we used a murine, in vitro ovarian cancer progression model in parallel with immortalized human cells to investigate how ovarian cancer cells of increasing aggressiveness respond to of fluid-induced shear stress. This biophysical stimulus significantly reduced cell viability in all cells exposed, independent of disease stage. Fluid shear stress induced spheroid formation and altered cytoskeleton organization in more tumorigenic cell lines. While benign ovarian cells appeared to survive in higher numbers under the influence of fluid shear stress, they exhibited severe morphological changes and chromosomal instability. These results suggest that exposure of benign cells to low magnitude fluid shear stress can induce phenotypic changes that are associated with transformation and ovarian cancer progression. Moreover, exposure of tumorigenic cells to fluid shear stress enhanced anchorage-independent survival, suggesting a role in promoting invasion and metastasis.

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

“…The progression of the disease is heavily dependent on the mammary tumor microenvironment (TME) which is comprised of a variety of dynamic stimuli, including shear, compression, tension and the surrounding three dimensional (3D) extracellular matrix (ECM) stiffness (Butcher, Alliston, & Weaver, ; DuFort, Paszek, & Weaver, ). To discover effective therapeutics, numerous in vitro models have been developed to isolate and explore the role of dynamic 3D stimuli within the TME (Bersini et al, ; Hyler et al, ; Li et al, ; Polacheck, German, Mammoto, Ingber, & Kamm, ; Rijal & Li, ; Rizvi et al, ; Shieh, Rozansky, Hinz, & Swartz, ; Sung et al, ; Weigelt, Ghajar, & Bissell, ).…”

Review: Mechanotransduction in ovarian cancer: Shearing into the unknown

“…Three murine ovarian cell lines ranging from benign to highly aggressive mouse ovarian cancer epithelial cells (MOSE), OCE1 (benign human), and SKOV3 (human ovarian clear cell adenocarcinoma) cell lines were exposed to fluid shear stress ranging from 0.13 to 0.32 dyn/cm 2 on a rotator plate for up to 12 days. 53 Fluid shear stress was shown to increase the capacity for spheroid formation in cell lines with a higher metastatic phenotype, increase the number of actin-containing protrusions and vinculin-containing focal adhesions for all cell types, as well as show nuclear change with an increase in multi-lobed nuclei and the number of tetraploid chromosomes in benign cell populations.…”

Fluid shear stress coupled with narrow constrictions induce cell type-dependent morphological and molecular changes in circulating tumor cells

“…Malignant cells appeared more resistant than non-malignant cells to shear stress 7,8 yet they still underwent significant apoptosis 9 , in particular as compared to hematopoietic cells. 10 Altered cytoskeleton organization in suspended and sheared primary ovarian cells was observed.…”