title: Role of platelet membrane glycoproteins Ib/IX and IIb/IIIa, and of platelet alpha-granule proteins in platelet aggregation induced by human osteosarcoma cells.
abstract: We have previously shown that the platelet-aggregating activity of human MG-63 and HOS osteosarcoma cells depends at least in part upon tumor cell surface-associated thrombospondin, and suggested that platelet-osteosarcoma cell interactions could occur through interactions with specific platelet membrane receptors. In this study, the platelet-aggregating activity of MG-63 and HOS cells was studied by using a variety of platelet disorders. Both osteosarcoma cell lines induced a biphasic platelet aggregation response when added to normal platelet-rich plasma, while the second phase of aggregation was absent when added to gray platelets (deficiency in alpha-granule proteins) and to aspirin-treated platelets. Platelets from two unrelated patients with type I Glanzmann's thrombasthenia (deficiency in glycoprotein (GP) GPIIb/IIIa) did not aggregate at all with osteosarcoma cells. Using giant platelets from three patients with Bernard-Soulier syndrome (deficiency in GPIb/IX), the aggregation response induced by MG-63 and HOS cells was monophasic and reversible when compared to normal-sized platelets and to giant platelets from a patient with May-Hegglin anomaly (no membrane GP defect). Because GPIb serves as a receptor for von Willebrand factor during hemostasis, aggregation experiments were also conducted with the platelet-rich plasma of two patients with a low plasma von Willebrand factor concentration (type I von Willebrand's disease) before and after the infusion of deamino-D-arginine vasopressin. MG-63 and HOS cells induced biphasic platelet aggregation both before and after deamino-D-arginine vasopressin treatment, while the ristocetin-dependent binding of von Willebrand factor to platelets only occurred after deamino-D-arginine vasopressin treatment. Preincubation of normal platelet-rich plasma with monoclonal antibody SZ-2 directed against the von Willebrand binding domain of GPIb did not inhibit the platelet-aggregation activity of osteosarcoma cells, whereas anti-GPIb antibody SZ-2 did inhibit ristocetin-induced platelet agglutination. In addition, anti-GPIX antibodies did not affect platelet-osteosarcoma cell interactions. In conclusion, our data demonstrate that the first phase of the platelet-aggregating activity of human osteosarcoma cells is initiated by the interaction of these tumor cells with platelet membrane GPIIb/IIIa, whereas the second phase, even if plasma von Willebrand factor is deficient, involves platelet membrane GPIb and the participation of platelet alpha-granule proteins in membrane-mediated events, making aggregation irreversible.
authors.affiliation: INSERM Research Unit 234, Hôpital Edouard Herriot, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Clezardin
authors.forename: J
authors.initials: J
authors.lastname: Drouin
authors.forename: M C
authors.initials: MC
authors.lastname: Morel-Kopp
authors.forename: M
authors.initials: M
authors.lastname: Hanss
authors.forename: B
authors.initials: B
authors.lastname: Kehrel
authors.forename: C M
authors.initials: CM
authors.lastname: Serre
authors.forename: C
authors.initials: C
authors.lastname: Kaplan
authors.forename: P D
authors.initials: PD
authors.lastname: Delmas
mesh_terms: D000911:Antibodies, Monoclonal; D001241:Aspirin / Q000494:pharmacology; D001606:Bernard-Soulier Syndrome / Q000097:blood*; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D002450:Cell Communication; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D019007:P-Selectin; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D012310:Ristocetin / Q000494:pharmacology; D013915:Thrombasthenia / Q000097:blood*; D019699:Thrombospondins; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D019699:Thrombospondins; D012310:Ristocetin; D001241:Aspirin