Document Detail

P-selectin mediates metastatic progression through binding to sulfatides on tumor cells.
MedLine Citation:
PMID:  17043066     Owner:  NLM     Status:  MEDLINE    
Hematogenous carcinoma metastasis is associated with tumor cell emboli formation, which is now known to be facilitated by selectins. P-selectin-mediated interactions of platelets with cancer cells are based mostly on mucin- and glycosaminoglycan-type selectin ligands. We previously showed that mouse colon carcinoma cells (MC-38) carry P-selectin ligands of nonmucin origin, which were not identified. Here we show that P-selectin ligands recognized on MC-38 cells are sulfated glycolipids, thereby facilitating experimental metastasis in a syngeneic mouse model. Metabolic inhibition of sulfation by incubation of cells with sodium chlorate almost completely abrogated P-selectin binding. Metabolic labeling of MC-38 cells with (35)S sulfate revealed only a single band as detected by high-performance thin layer chromatography analysis of a total lipid extract. Matrix-assisted laser desorption/ionization tandem time-of-flight/time-of-flight analysis (MALDI-TOF-TOF) analysis of the purified sulfate-containing lipid fraction identified the selectin ligand to be a sulfated galactosylceramide SM4 (HSO(3)-3Galbeta-1Cer). Modulation of glycolipid biosynthesis in MC-38 cells altered P-selectin binding, thereby confirming sulfoglycolipids to be major P-selectin ligands. In addition, P-selectin was also found to recognize lactosylceramide sulfate SM3 (HSO(3)-3Galbeta-4Glcbeta-1Cer) and gangliotriaosylceramide sulfate SM2 [GalNAcbeta-4(HSO(3)-3)Galbeta-4Glcbeta-1Cer] in human hepatoma cells. Finally, the enzymatic removal of sulfation from the cell surface of MC-38 cells resulted in decreased P-selectin binding and led to attenuation of metastasis. Thus, SM4 sulfatide serves as a native ligand for P-selectin contributing to cell-cell interactions and to facilitation of metastasis.
Josep Garcia; Nico Callewaert; Lubor Borsig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-16
Journal Detail:
Title:  Glycobiology     Volume:  17     ISSN:  0959-6658     ISO Abbreviation:  Glycobiology     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-11     Completed Date:  2007-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  185-96     Citation Subset:  IM    
Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.
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MeSH Terms
Carcinoma / chemistry,  metabolism,  pathology*
Cell Communication*
Disease Progression
Neoplasm Metastasis
P-Selectin / metabolism*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Sulfoglycosphingolipids / analysis,  metabolism*
Tumor Cells, Cultured
Reg. No./Substance:
0/Ligands; 0/P-Selectin; 0/Sulfoglycosphingolipids

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