Issue 11, 2013

Bioactive sphingolipid metabolites modulate ovarian cancer cell structural mechanics

Abstract

Cancer progression is associated with an increased deformability of cancer cells and reduced resistance to mechanical forces, enabling motility and invasion. This is important for metastases survival and outgrowth and as such could be a target for chemopreventive strategies. In this study, we determined the differential effects of exogenous sphingolipid metabolites on the elastic modulus of mouse ovarian surface epithelial cells as they transition to cancer. Treatment with ceramide or sphingosine-1-phosphate in non-toxic concentrations decreased the average elastic modulus by 21% (p ≤ 0.001) in transitional and 15% (p ≤ 0.02) in aggressive stages while exerting no appreciable effect on non-malignant cells. In contrast, sphingosine treatment on average increased the elastic modulus by 33% (p ≤ 0.0002) in aggressive cells while not affecting precursor cells. These results indicate that tumor-supporting sphingolipid metabolites act by making cells softer, while the anti-cancer metabolite sphingosine partially reverses the decreased elasticity associated with cancer progression. Thus, sphingosine may be a valid alternative to conventional chemotherapeutics in ovarian cancer prevention or treatment.

Graphical abstract: Bioactive sphingolipid metabolites modulate ovarian cancer cell structural mechanics

Article information

Article type
Paper
Submitted
12 Jun 2013
Accepted
22 Aug 2013
First published
28 Aug 2013

Integr. Biol., 2013,5, 1385-1392

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