Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells.
Sphingosylphosphorylcholine (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.
Beil
Michael
M
Department of Internal Medicine I, University of Ulm, 89071 Ulm, Germany.
Micoulet
Alexandre
A
von Wichert
Götz
G
Paschke
Stephan
S
Walther
Paul
P
Omary
M Bishr
MB
Van Veldhoven
Paul P
PP
Gern
Ulrike
U
Wolff-Hieber
Elke
E
Eggermann
Juliane
J
Waltenberger
Johannes
J
Adler
Guido
G
Spatz
Joachim
J
Seufferlein
Thomas
T
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002277:Carcinoma / Q000378:metabolism* / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004548:Elasticity / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D007633:Keratins / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009362:Neoplasm Metastasis / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D007633:Keratins; D013110:Sphingosine