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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 [Formula: see text] 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.

SUBMITTER: Hyler AR

PROVIDER: S-EPMC5864000 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Hyler Alexandra R AR Baudoin Nicolaas C NC Brown Megan S MS Stremler Mark A MA Cimini Daniela D Davalos Rafael V RV Schmelz Eva M EM

PloS one 20180322 3

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 [Formula: see text] of fluid-induced shear stress. This biophysical stimulus significantly ...[more]

PMID: 29566010

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Project description:Pluripotent embryonic stem cells (ESCs) are capable of differentiating into all mesoderm-derived cell lineages, including endothelial, hematopoietic, and cardiac cell types. Common strategies to direct mesoderm differentiation of ESCs rely on exposing the cells to a series of biochemical and biophysical cues at different stages of differentiation to promote maturation toward specific cell phenotypes. Shear forces that mimic cardiovascular physiological forces can evoke a myriad of responses in somatic and stem cell populations, and have, thus, been studied as a means to direct stem cell differentiation. However, elucidating the effects of shear pre-conditioning on the subsequent vascular differentiation and morphogenesis of ESCs has yet to be examined. In this study, ESC monolayers were subjected to physiological shear (5 dyn/cm(2)) or static conditions for 2 days on collagen IV-coated substrates before initiating embryoid body (EB) differentiation. Immediately after the pre-conditioning period, shear pre-conditioned and statically cultured ESCs exhibited similar morphologies and largely retained a pluripotent phenotype; however, ESCs exposed to fluid shear expressed increased levels of endothelial marker genes Flk-1 (∼3-fold), VE-cadherin (∼3-fold), and PECAM (∼2-fold), compared with statically cultured ESCs. After 7 days of EB culture, ∼70% of EBs formed from shear pre-conditioned ESCs expressed significantly higher levels of endothelial marker genes compared with EBs formed from statically cultured ESCs. Interestingly, unlike EBs formed from statically cultured ESCs, EBs formed from fluid shear stress pre-conditioned ESCs exhibited a centrally localized region of VE-cadherin(+) cells that persisted for at least 10 days of differentiation. These results demonstrate that fluid shear stress pre-conditioning not only promotes ESC endothelial gene expression but also subsequently impacts the organization of endothelial cells within EBs. Together, these studies highlight a novel approach to promote in vitro morphogenesis of developmental vasculogenic models and potentially promote pre-vascularization of tissue-engineered constructs derived from pluripotent stem cells.

Dataset Information

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

Publications

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

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