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

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.