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P-selectin mediates metastatic progression through binding to sulfatides on tumor cells

(2007) GLYCOBIOLOGY. 17(2). p.185-196
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Abstract
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 S-35 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 (HSO3-3Gal beta-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 (HSO3-3Gal beta-4Glc beta-1Cer) and gangliotriaosylceramide sulfate SM2 [GalNAc beta-4(HSO3-3)Gal beta-4Glc beta-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.
Keywords
LEWIS LUNG-CARCINOMA, ABERRANT GLYCOSYLATION, COLORECTAL-CANCER, OVARIAN-TUMORS, EXPRESSION, GLYCOSPHINGOLIPIDS, LIGANDS, CARBOHYDRATE, GLYCOLIPIDS, ADHESION, carbohydrate sulfation, glycolipids, MALDI-TOF, metastasis, selectin

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Citation

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Chicago
Garcia, Josep, Nico Callewaert, and Lubor Borsig. 2007. “P-selectin Mediates Metastatic Progression Through Binding to Sulfatides on Tumor Cells.” Glycobiology 17 (2): 185–196.
APA
Garcia, J., Callewaert, N., & Borsig, L. (2007). P-selectin mediates metastatic progression through binding to sulfatides on tumor cells. GLYCOBIOLOGY, 17(2), 185–196.
Vancouver
1.
Garcia J, Callewaert N, Borsig L. P-selectin mediates metastatic progression through binding to sulfatides on tumor cells. GLYCOBIOLOGY. 2007;17(2):185–96.
MLA
Garcia, Josep, Nico Callewaert, and Lubor Borsig. “P-selectin Mediates Metastatic Progression Through Binding to Sulfatides on Tumor Cells.” GLYCOBIOLOGY 17.2 (2007): 185–196. Print.
@article{1203439,
  abstract     = {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 S-35 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 (HSO3-3Gal beta-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 (HSO3-3Gal beta-4Glc beta-1Cer) and gangliotriaosylceramide sulfate SM2 [GalNAc beta-4(HSO3-3)Gal beta-4Glc beta-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.},
  author       = {Garcia, Josep and Callewaert, Nico and Borsig, Lubor},
  issn         = {0959-6658},
  journal      = {GLYCOBIOLOGY},
  keywords     = {LEWIS LUNG-CARCINOMA,ABERRANT GLYCOSYLATION,COLORECTAL-CANCER,OVARIAN-TUMORS,EXPRESSION,GLYCOSPHINGOLIPIDS,LIGANDS,CARBOHYDRATE,GLYCOLIPIDS,ADHESION,carbohydrate sulfation,glycolipids,MALDI-TOF,metastasis,selectin},
  language     = {eng},
  number       = {2},
  pages        = {185--196},
  title        = {P-selectin mediates metastatic progression through binding to sulfatides on tumor cells},
  url          = {http://dx.doi.org/10.1093/glycob/cw1059},
  volume       = {17},
  year         = {2007},
}

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