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Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time
Published on: May 20, 2014
Roles of bioactive sphingolipid metabolites in ovarian cancer cell biomechanics
Hesam Babahosseini1, Paul C Roberts, Eva M Schmelz
1VT MEMS Lab, Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA, USA. hbabahosseini@vt.edu
Abstract:
Bioactive sphingolipid metabolites have emerged as important lipid second messengers in the regulation of cell growth, death, motility and many other events. These processes are important in cancer development and progression; thus, sphingolipid metabolites have been implicated in both cancer development and cancer prevention. Despite recent considerable progress in understanding the multi-faceted functions of these bioactive metabolites, little is known about their influence on the biomechanical property of cells. The biomechanical properties of cancer cells change during progression with aggressive and invasive cells being softer compared to their benign counterparts. In this paper, we investigated the effects of exogenous sphingolipid metabolites on the Young's modulus and cytoskeletal organization of cells representing aggressive ovarian cancer. Our findings demonstrate that the elasticity of aggressive ovarian cancer cells decreased ∼15% after treatment with ceramide and sphingosine-1-phosphate. In contrast, sphingosine treatment caused a ∼30% increase in the average elasticity which was associated with a more defined actin cytoskeleton organization. This indicates that sphingolipid metabolites differentially modulate the biomechanic properties of cancer cells which may have a critical impact on cancer cell survival and progression, and the use of sphingolipid metabolites as chemopreventive or chemo-therapeutic agents.
Insights
Bioactive sphingolipid metabolites, like ceramide and sphingosine-1-phosphate, alter cancer cell mechanics. These findings suggest sphingolipids could be new cancer therapies by changing cell elasticity and survival.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Bioactive sphingolipids are crucial lipid second messengers regulating cell functions like growth and death.
- These metabolites play roles in cancer development and prevention, but their impact on cell biomechanics is largely unknown.
- Cancer cell biomechanical properties, such as softness, correlate with aggressiveness and invasiveness.
Purpose of the Study:
- To investigate the effects of exogenous sphingolipid metabolites on the biomechanical properties and cytoskeletal organization of aggressive ovarian cancer cells.
- To determine how specific sphingolipids influence cell elasticity (Young's modulus) and actin cytoskeleton structure.
Main Methods:
- Treatment of aggressive ovarian cancer cells with exogenous sphingolipid metabolites (ceramide, sphingosine-1-phosphate, sphingosine).
- Measurement of cell elasticity using Young's modulus.
- Assessment of cytoskeletal organization, specifically actin filaments.
Main Results:
- Ceramide and sphingosine-1-phosphate treatments decreased ovarian cancer cell elasticity by approximately 15%.
- Sphingosine treatment increased cell elasticity by approximately 30% and enhanced actin cytoskeleton organization.
- Sphingolipid metabolites differentially modulate cancer cell biomechanical properties.
Conclusions:
- Sphingolipid metabolites significantly alter the biomechanical properties of aggressive ovarian cancer cells.
- These modulations in cell elasticity and cytoskeletal organization may impact cancer cell survival and progression.
- Sphingolipid metabolites show potential as chemopreventive or chemotherapeutic agents by targeting cancer cell mechanics.

