title: Effect of tumor gangliosides on tyrosine phosphorylation of p125FAK             in platelet adhesion to collagen.
abstract: The exact mechanisms as to how platelets influence blood-borne metastasis             remain poorly understood. Gangliosides, sialic acid-containing glycosphingolipids,             are associated with tumor progression and metastasis in humans. Gangliosides isolated             from tumor cells promote collagen-stimulated platelet aggregation and ATP secretion             and enhance platelet adhesion to immobilized collagen. Gangliosides interact with             a number of cell surface receptors including integrin receptors. In this study,             we examined the effects of α2β1 integrin-mediated platelet adhesion to collagen             and phosphotyrosine signaling of focal adhesion kinase, p125FAK (FAK). platelets             pre-incubated with neuroblastoma tumor gangliosides (NBTGs) or their major component             GD2 (disialoganglioside) were more adherent to immobilized collagen (OD570 0.43±0.12,             0.39±0.13) compared to platelets pre-incubated with MTB (0.14±0.06, p<0.001);             the effect of NBTGs was blocked by F-17 anti-α2 antibody. Pre-incubation of platelets             with NBTGs resulted in a marked increase in the phosphotyrosine content of p125FAK             in the adherent platelets compared to the MTB-pre-incubated adherent platelets.             F-17 anti-α2 antibody decreased protein tyrosine phosphorylation of NBTG-incubated             platelets adherent to collagen. These results indicate that the tumor gangliosides             enhance platelet adhesion to extracellular matrix collagen by upregulating integrin             α2β1-mediated tyrosine phosphorylation of p125FAK, thereby providing insight into             how this interaction may be involved in neuroblastoma metastasis.
authors.affiliation: Cancer Institute, the Second Clinical College of Medicine, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong 51802, PR China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Chen
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Chen
authors.forename: Chang-Gang
authors.initials: CG
authors.lastname: Li
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Yue
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Mai
authors.forename: Fei-Qiu
authors.initials: FQ
authors.lastname: Wen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D005732:Gangliosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D005732:Gangliosides; D038982:Integrin alpha2beta1; D019000:Phosphotyrosine; D003094:Collagen; D051417:Focal Adhesion Kinase 1