Nature Cell Biology
5, 803 - 811 (2003)
Published online: 24 August 2003; | doi:10.1038/ncb1037
Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cellsMichael Beil1, 8, Alexandre Micoulet2, 8, Götz von Wichert3, Stephan Paschke1, 8, Paul Walther4, M. Bishr Omary5, Paul P. Van Veldhoven6, Ulrike Gern1, 8, Elke Wolff-Hieber1, 8, Juliane Eggermann7, Johannes Waltenberger7, Guido Adler1, 8, Joachim Spatz2, 8
& Thomas Seufferlein1, 81
Department of Internal Medicine I, University of Ulm, 89071 Ulm, Germany. 2
Department of Physical Chemistry, Biophysical Chemistry Section, University of Heidelberg, 69120 Heidelberg, Germany. 3
Department of Biological Sciences, Columbia University, New York, NY 10027, USA. 4
Department of Electron Microscopy, University of Ulm, 89071 Ulm, Germany. 5
Department of Medicine, VA Palo Alto Health Care System and Stanford University, Palo Alto, California, CA 94304, USA. 6
Afdeling Farmakologie, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. 7
Department of Internal Medicine II, University of Ulm, 89071 Ulm, Germany. 8
The groups of the Department. of Internal Medicine I, Ulm and the Department. of Physical Chemistry, Heidelberg contributed equally to this manuscript.
Correspondence should be addressed to Thomas Seufferlein thomas.seufferlein@medizin.uni-ulm.deSphingosylphosphorylcholine (SPC) is a naturally occurring bioactive lipid that is present in high density lipoproteins (HDL) particles and found at increased levels in blood and malignant ascites of patients with ovarian cancer. Here, we show that incubation of human epithelial tumour cells with SPC induces a perinuclear reorganization of intact keratin 8−18 filaments. This effect is specific for SPC, largely independent of F-actin and microtubules, and is accompanied by keratin phosphorylation. In vivo visco-elastic probing of single cancer cells demonstrates that SPC increases cellular elasticity. Accordingly, SPC stimulates migration of cells through size-limited pores in a more potent manner than lysophosphatidic acid (LPA). LPA induces actin stress fibre formation, but does not reorganize keratins in cancer cells and hence increases cellular stiffness. We propose that reorganization of keratin by SPC may facilitate biological phenomena that require a high degree of elasticity, such as squeezing of cells through membranous pores during metastasis.
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